A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (LUCERNE)

• ClinicalTrials.gov Identifier: NCT03823300
• Recruitment Status: Completed
• First Posted: January 30, 2019
• Results First Posted: May 4, 2022
• Last Update Posted: January 13, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Wet Macular Degeneration
• Interventions: Drug: Faricimab; Drug: Aflibercept; Procedure: Sham Procedure
• Enrollment: 658

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 1012 patients were screened, 354 of whom failed screening, most commonly due to not meeting inclusion criteria. A total of 658 treatment-naive patients with nAMD were randomized 1:1 into the study: 331 to the faricimab arm and 327 to the aflibercept arm.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Period Title: Overall Study
Started [1]	331	327
Received at Least One Dose of Study Drug [2]	331	326
Completed up to Week 48 [3]	321	309
Completed	297	273
Not Completed	34	54
Reason Not Completed
Withdrawal by Subject	16	22
Death	10	14
Adverse Event	3	5
Physician Decision	1	7
Lost to Follow-up	1	3
Protocol Violation	1	1
Lack of Efficacy	1	1
Not Eligible	0	1
Other	1	0
[1] Intent-to-Treat (ITT) Population; [2] Safety Population; [3] Primary Completion Date Cutoff

Baseline Characteristics

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept	Total
Arm/Group Description		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).	Total of all reporting groups
Overall Number of Baseline Participants		331	327	658
Baseline Analysis Population Description		Intent-to-Treat (ITT) Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	331 participants	327 participants	658 participants
		74.8 (8.4)	76.1 (8.6)	75.5 (8.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	Female	203 61.3%	188 57.5%	391 59.4%
	Male	128 38.7%	139 42.5%	267 40.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	Hispanic or Latino	35 10.6%	46 14.1%	81 12.3%
	Not Hispanic or Latino	287 86.7%	274 83.8%	561 85.3%
	Unknown or Not Reported	9 2.7%	7 2.1%	16 2.4%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	White	278 84.0%	270 82.6%	548 83.3%
	Asian	38 11.5%	34 10.4%	72 10.9%
	Unknown	12 3.6%	17 5.2%	29 4.4%
	Black or African American	2 0.6%	5 1.5%	7 1.1%
	American Indian or Alaska Native	1 0.3%	0 0.0%	1 0.2%
	Multiple	0 0.0%	1 0.3%	1 0.2%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	United States and Canada	135 40.8%	132 40.4%	267 40.6%
	Asia	35 10.6%	33 10.1%	68 10.3%
	Rest of the World	161 48.6%	162 49.5%	323 49.1%
Number of Participants by the Eye (Right or Left) Chosen as the Study Eye; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	Right Eye	168 50.8%	170 52.0%	338 51.4%
	Left Eye	163 49.2%	157 48.0%	320 48.6%
Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye [1]; Mean (Standard Deviation); Unit of measure: ETDRS Letters
	Number Analyzed	331 participants	327 participants	658 participants
		58.7 (14.0)	58.9 (13.3)	58.8 (13.6)
		[1] Measure Description: Best corrected visual acuity (BCVA) at a starting test distance of 4 meters was measured using a set of three Precision VisionTM or Lighthouse distance acuity charts (modified ETDRS Charts 1, 2, and R). The BCVA letter score ranges from 0 to 100 (best score attainable), with a higher score indicating better visual acuity.
Number of Participants by the BCVA Letter Score Categories in the Study Eye; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	≥74 Letters	45 13.6%	39 11.9%	84 12.8%
	73 to 55 Letters	181 54.7%	183 56.0%	364 55.3%
	≤54 Letters	105 31.7%	105 32.1%	210 31.9%
Number of Participants by the Low Luminance Deficit (LLD) Letter Score Categories in the Study Eye; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	<33 Letters	238 71.9%	234 71.6%	472 71.7%
	≥33 Letters	89 26.9%	93 28.4%	182 27.7%
	Missing/Invalid	4 1.2%	0 0.0%	4 0.6%
Choroidal Neovascularization (CNV) Lesion Type in the Study Eye by Fundus Fluorescein Angiography; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	331 participants	327 participants	658 participants
	Occult	171 51.7%	140 42.8%	311 47.3%
	Classic	98 29.6%	109 33.3%	207 31.5%
	Minimally Classic	30 9.1%	31 9.5%	61 9.3%
	Retinal Angiomatous Proliferation (RAP)	14 4.2%	15 4.6%	29 4.4%
	Predominantly Classic	6 1.8%	16 4.9%	22 3.3%
	Polypoidal Choroidal Vasculopathy (PCV)	5 1.5%	8 2.4%	13 2.0%
	Missing	7 2.1%	8 2.4%	15 2.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
Time Frame	From Baseline through Week 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: ETDRS Letters
	6.6; (5.3 to 7.8)	6.6; (5.3 to 7.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	The null hypothesis, H0: μ(faricimab) - μ(aflibercept) ≤-4 letters; the alternative hypothesis, Ha: μ(faricimab) - μ(aflibercept) >-4 letters. A sample size of approximately 320 participants in each arm provided greater than 90% power to show non-inferiority of faricimab to aflibercept in the change from baseline BCVA averaged over Weeks 40, 44, and 48 in the ITT population, using a non-inferiority margin of 4 letters at the one-sided 0.02485 significance level.
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower bound of a two-sided 95.03% confidence interval (CI) for the difference in adjusted means of the two treatments (faricimab minus aflibercept) is greater than -4 letters (the non-inferiority margin), then faricimab is considered non-inferior to aflibercept.
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.7 to 1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments	The treatment difference in adjusted means of change from baseline BCVA is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept. MMRM adjustments are listed in the outcome measure description.

2. Secondary Outcome

Title	Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
Time Frame	From Baseline through Week 60

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: ETDRS Letters
	6.6; (5.3 to 7.9)	7.1; (5.8 to 8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in Adjusted Means at Weeks 52-60
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -2.4 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.93
	Estimation Comments	The treatment difference in adjusted means of change from baseline BCVA is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept. MMRM adjustments are listed in the outcome measure description.

3. Secondary Outcome

Title	Change From Baseline in BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (≥74, 73-55, and ≤54 letters), baseline LLD (<33 and ≥33 letters), and region (U.S. and Canada, Asia, and rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% CI is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: ETDRS Letters
Week 4	5.1; (4.2 to 5.9)	4.3; (3.5 to 5.2)
Week 8	6.0; (5.1 to 6.9)	5.8; (4.9 to 6.8)
Week 12	7.0; (6.1 to 8.0)	6.4; (5.4 to 7.4)
Week 16	6.7; (5.6 to 7.7)	6.4; (5.4 to 7.4)
Week 20	7.0; (5.9 to 8.1)	6.8; (5.7 to 7.9)
Week 24	7.0; (5.8 to 8.1)	6.5; (5.4 to 7.6)
Week 28	7.1; (5.9 to 8.2)	6.8; (5.6 to 7.9)
Week 32	7.2; (6.0 to 8.3)	6.9; (5.7 to 8.0)
Week 36	6.7; (5.5 to 7.9)	6.8; (5.6 to 8.0)
Week 40	6.8; (5.5 to 8.1)	6.7; (5.4 to 8.0)
Week 44	6.5; (5.3 to 7.8)	6.4; (5.2 to 7.7)
Week 48	6.5; (5.1 to 7.8)	6.4; (5.0 to 7.7)
Week 52	6.4; (5.1 to 7.7)	6.9; (5.5 to 8.3)
Week 56	7.1; (5.7 to 8.4)	7.4; (6.0 to 8.7)
Week 60	6.3; (4.9 to 7.7)	6.9; (5.5 to 8.3)
Week 64	6.5; (5.1 to 8.0)	6.1; (4.7 to 7.6)
Week 68	6.2; (4.8 to 7.6)	6.7; (5.3 to 8.1)
Week 72	6.4; (4.9 to 7.8)	6.2; (4.8 to 7.7)
Week 76	6.4; (4.9 to 7.9)	6.0; (4.6 to 7.5)
Week 80	5.9; (4.4 to 7.4)	5.6; (4.1 to 7.2)
Week 84	5.9; (4.3 to 7.5)	5.8; (4.2 to 7.3)
Week 88	5.6; (4.1 to 7.1)	5.4; (3.9 to 7.0)
Week 92	5.7; (4.2 to 7.2)	5.4; (3.9 to 7.0)
Week 96	5.4; (3.9 to 7.0)	5.5; (3.9 to 7.0)
Week 100	5.2; (3.6 to 6.8)	4.9; (3.3 to 6.5)
Week 104	5.0; (3.4 to 6.6)	5.3; (3.7 to 6.9)
Week 108	5.2; (3.5 to 6.8)	5.4; (3.7 to 7.0)
Week 112	4.8; (3.2 to 6.5)	4.8; (3.1 to 6.5)

4. Secondary Outcome

Title	Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 40, 44, and 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	302	291
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Gaining ≥15 Letters	20.2; (15.9 to 24.6)	22.2; (17.7 to 26.8)
Gaining ≥10 Letters	39.2; (34.1 to 44.4)	35.8; (30.6 to 40.9)
Gaining ≥5 Letters	60.5; (55.2 to 65.7)	59.4; (53.9 to 64.9)
Gaining ≥0 Letters	82.2; (77.9 to 86.4)	79.1; (74.5 to 83.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Gaining ≥15 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -8.3 to 4.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥15 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Gaining ≥10 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; -3.9 to 10.7
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥10 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Gaining ≥5 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -6.6 to 8.6
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥5 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Gaining ≥0 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -3.1 to 9.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥0 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

5. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
Description	BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 52, 56, and 60

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 52, 56, or 60 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	289	276
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	22.6; (18.1 to 27.1)	23.7; (19.1 to 28.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in CMH Weighted Percentages at Weeks 52-60
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -7.7 to 5.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥15 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

6. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		10.5; (7.2 to 13.7)	9.5; (6.4 to 12.6)
Week 8	Number Analyzed	327 participants	322 participants
		13.9; (10.3 to 17.5)	13.5; (10.0 to 17.1)
Week 12	Number Analyzed	326 participants	317 participants
		17.7; (13.7 to 21.6)	17.2; (13.3 to 21.1)
Week 16	Number Analyzed	321 participants	315 participants
		17.3; (13.3 to 21.3)	17.7; (13.6 to 21.8)
Week 20	Number Analyzed	320 participants	309 participants
		20.2; (15.9 to 24.4)	20.2; (15.9 to 24.4)
Week 24	Number Analyzed	295 participants	288 participants
		19.3; (14.9 to 23.6)	18.9; (14.6 to 23.3)
Week 28	Number Analyzed	292 participants	271 participants
		23.7; (19.1 to 28.3)	20.8; (16.1 to 25.4)
Week 32	Number Analyzed	287 participants	288 participants
		22.6; (18.0 to 27.2)	19.5; (15.1 to 23.9)
Week 36	Number Analyzed	293 participants	283 participants
		22.2; (17.7 to 26.6)	20.6; (16.1 to 25.0)
Week 40	Number Analyzed	286 participants	288 participants
		23.7; (19.0 to 28.3)	25.4; (20.6 to 30.1)
Week 44	Number Analyzed	285 participants	273 participants
		21.5; (17.1 to 26.0)	22.4; (17.7 to 27.1)
Week 48	Number Analyzed	282 participants	277 participants
		22.3; (17.7 to 26.9)	23.1; (18.3 to 27.8)
Week 52	Number Analyzed	283 participants	273 participants
		22.7; (18.1 to 27.2)	23.4; (18.7 to 28.1)
Week 56	Number Analyzed	283 participants	273 participants
		25.9; (21.1 to 30.7)	27.0; (22.0 to 32.0)
Week 60	Number Analyzed	278 participants	273 participants
		22.6; (18.1 to 27.1)	25.8; (20.9 to 30.7)
Week 64	Number Analyzed	276 participants	266 participants
		25.4; (20.6 to 30.2)	21.2; (16.5 to 25.9)
Week 68	Number Analyzed	276 participants	266 participants
		24.5; (19.7 to 29.3)	24.9; (20.0 to 29.8)
Week 72	Number Analyzed	276 participants	261 participants
		22.6; (17.9 to 27.2)	27.1; (22.0 to 32.1)
Week 76	Number Analyzed	268 participants	267 participants
		22.1; (17.4 to 26.8)	24.9; (20.1 to 29.8)
Week 80	Number Analyzed	275 participants	264 participants
		22.9; (18.1 to 27.7)	25.8; (20.8 to 30.7)
Week 84	Number Analyzed	279 participants	254 participants
		23.7; (18.9 to 28.5)	25.6; (20.6 to 30.6)
Week 88	Number Analyzed	276 participants	253 participants
		24.1; (19.3 to 29.0)	24.4; (19.5 to 29.3)
Week 92	Number Analyzed	273 participants	253 participants
		22.5; (17.8 to 27.2)	24.8; (19.9 to 29.8)
Week 96	Number Analyzed	266 participants	247 participants
		25.7; (20.8 to 30.6)	25.5; (20.5 to 30.6)
Week 100	Number Analyzed	272 participants	254 participants
		24.8; (19.9 to 29.8)	23.1; (18.3 to 28.0)
Week 104	Number Analyzed	263 participants	249 participants
		22.5; (17.7 to 27.3)	24.6; (19.6 to 29.5)
Week 108	Number Analyzed	267 participants	247 participants
		21.6; (16.8 to 26.3)	22.3; (17.5 to 27.1)
Week 112	Number Analyzed	267 participants	254 participants
		25.2; (20.3 to 30.1)	22.5; (17.8 to 27.1)

7. Secondary Outcome

Title	Percentage of Participants Gaining ≥10 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		24.2; (19.8 to 28.7)	22.1; (17.7 to 26.5)
Week 8	Number Analyzed	327 participants	322 participants
		32.4; (27.5 to 37.2)	28.7; (24.1 to 33.4)
Week 12	Number Analyzed	326 participants	317 participants
		34.2; (29.3 to 39.1)	34.6; (29.5 to 39.7)
Week 16	Number Analyzed	321 participants	315 participants
		35.3; (30.3 to 40.4)	34.2; (29.2 to 39.3)
Week 20	Number Analyzed	320 participants	309 participants
		37.8; (32.7 to 42.9)	34.3; (29.2 to 39.4)
Week 24	Number Analyzed	295 participants	288 participants
		39.2; (33.8 to 44.5)	35.2; (29.9 to 40.5)
Week 28	Number Analyzed	292 participants	271 participants
		40.5; (35.1 to 45.8)	36.0; (30.5 to 41.4)
Week 32	Number Analyzed	287 participants	288 participants
		40.5; (35.1 to 46.0)	35.0; (29.7 to 40.3)
Week 36	Number Analyzed	293 participants	283 participants
		38.9; (33.6 to 44.2)	38.9; (33.5 to 44.3)
Week 40	Number Analyzed	286 participants	288 participants
		40.9; (35.5 to 46.3)	39.3; (34.0 to 44.7)
Week 44	Number Analyzed	285 participants	273 participants
		42.3; (36.8 to 47.8)	39.5; (34.1 to 45.0)
Week 48	Number Analyzed	282 participants	277 participants
		41.0; (35.5 to 46.5)	38.6; (33.2 to 43.9)
Week 52	Number Analyzed	283 participants	273 participants
		44.2; (38.8 to 49.7)	42.1; (36.6 to 47.6)
Week 56	Number Analyzed	283 participants	273 participants
		44.2; (38.8 to 49.7)	43.6; (38.1 to 49.2)
Week 60	Number Analyzed	278 participants	273 participants
		43.1; (37.6 to 48.6)	42.4; (36.8 to 47.9)
Week 64	Number Analyzed	276 participants	266 participants
		44.0; (38.5 to 49.5)	41.1; (35.4 to 46.8)
Week 68	Number Analyzed	276 participants	266 participants
		40.1; (34.7 to 45.5)	40.7; (35.3 to 46.2)
Week 72	Number Analyzed	276 participants	261 participants
		42.0; (36.5 to 47.4)	38.9; (33.4 to 44.3)
Week 76	Number Analyzed	268 participants	267 participants
		42.2; (36.7 to 47.8)	40.7; (35.1 to 46.2)
Week 80	Number Analyzed	275 participants	264 participants
		44.2; (38.6 to 49.9)	41.9; (36.2 to 47.6)
Week 84	Number Analyzed	279 participants	254 participants
		42.7; (37.2 to 48.3)	41.4; (35.6 to 47.2)
Week 88	Number Analyzed	276 participants	253 participants
		40.3; (34.8 to 45.9)	39.4; (33.7 to 45.1)
Week 92	Number Analyzed	273 participants	253 participants
		42.1; (36.5 to 47.8)	41.0; (35.3 to 46.7)
Week 96	Number Analyzed	266 participants	247 participants
		41.1; (35.5 to 46.7)	39.1; (33.3 to 45.0)
Week 100	Number Analyzed	272 participants	254 participants
		40.2; (34.6 to 45.7)	34.6; (29.0 to 40.1)
Week 104	Number Analyzed	263 participants	249 participants
		44.0; (38.3 to 49.7)	36.2; (30.5 to 41.9)
Week 108	Number Analyzed	267 participants	247 participants
		41.7; (36.0 to 47.4)	38.0; (32.2 to 43.8)
Week 112	Number Analyzed	267 participants	254 participants
		41.3; (35.7 to 47.0)	35.0; (29.6 to 40.5)

8. Secondary Outcome

Title	Percentage of Participants Gaining ≥5 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		47.8; (42.6 to 53.0)	47.5; (42.2 to 52.8)
Week 8	Number Analyzed	327 participants	322 participants
		56.8; (51.6 to 62.0)	54.6; (49.3 to 59.8)
Week 12	Number Analyzed	326 participants	317 participants
		63.9; (58.9 to 68.9)	57.6; (52.3 to 62.9)
Week 16	Number Analyzed	321 participants	315 participants
		61.7; (56.5 to 66.8)	59.6; (54.3 to 64.9)
Week 20	Number Analyzed	320 participants	309 participants
		64.1; (59.0 to 69.2)	60.9; (55.6 to 66.3)
Week 24	Number Analyzed	295 participants	288 participants
		62.2; (56.8 to 67.6)	60.2; (54.7 to 65.7)
Week 28	Number Analyzed	292 participants	271 participants
		63.6; (58.2 to 68.9)	60.5; (54.8 to 66.2)
Week 32	Number Analyzed	287 participants	288 participants
		63.3; (58.0 to 68.7)	60.1; (54.6 to 65.6)
Week 36	Number Analyzed	293 participants	283 participants
		61.4; (56.0 to 66.9)	60.4; (54.9 to 65.9)
Week 40	Number Analyzed	286 participants	288 participants
		63.5; (58.1 to 68.9)	60.9; (55.5 to 66.4)
Week 44	Number Analyzed	285 participants	273 participants
		60.1; (54.6 to 65.6)	62.3; (56.7 to 67.8)
Week 48	Number Analyzed	282 participants	277 participants
		60.0; (54.5 to 65.6)	63.5; (57.9 to 69.1)
Week 52	Number Analyzed	283 participants	273 participants
		63.5; (58.1 to 69.0)	67.2; (61.7 to 72.6)
Week 56	Number Analyzed	283 participants	273 participants
		64.1; (58.7 to 69.5)	66.5; (61.0 to 72.0)
Week 60	Number Analyzed	278 participants	273 participants
		61.6; (56.1 to 67.2)	65.5; (59.9 to 71.0)
Week 64	Number Analyzed	276 participants	266 participants
		65.2; (59.8 to 70.6)	63.1; (57.5 to 68.8)
Week 68	Number Analyzed	276 participants	266 participants
		63.0; (57.4 to 68.5)	64.0; (58.5 to 69.6)
Week 72	Number Analyzed	276 participants	261 participants
		64.1; (58.6 to 69.6)	66.6; (60.9 to 72.2)
Week 76	Number Analyzed	268 participants	267 participants
		63.9; (58.2 to 69.6)	58.7; (53.0 to 64.4)
Week 80	Number Analyzed	275 participants	264 participants
		63.3; (57.7 to 68.9)	62.3; (56.6 to 67.9)
Week 84	Number Analyzed	279 participants	254 participants
		61.6; (56.1 to 67.2)	64.3; (58.6 to 70.1)
Week 88	Number Analyzed	276 participants	253 participants
		62.6; (57.1 to 68.1)	60.7; (54.9 to 66.5)
Week 92	Number Analyzed	273 participants	253 participants
		62.7; (57.1 to 68.3)	58.3; (52.6 to 64.0)
Week 96	Number Analyzed	266 participants	247 participants
		61.3; (55.6 to 67.0)	61.0; (55.1 to 67.0)
Week 100	Number Analyzed	272 participants	254 participants
		61.7; (56.1 to 67.3)	56.9; (50.9 to 62.9)
Week 104	Number Analyzed	263 participants	249 participants
		60.3; (54.6 to 66.0)	59.3; (53.3 to 65.3)
Week 108	Number Analyzed	267 participants	247 participants
		62.4; (56.8 to 68.0)	58.0; (51.8 to 64.1)
Week 112	Number Analyzed	267 participants	254 participants
		59.9; (54.2 to 65.6)	59.4; (53.4 to 65.3)

9. Secondary Outcome

Title	Percentage of Participants Gaining ≥0 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		80.5; (76.3 to 84.7)	74.2; (69.5 to 78.9)
Week 8	Number Analyzed	327 participants	322 participants
		82.3; (78.3 to 86.3)	80.3; (76.0 to 84.5)
Week 12	Number Analyzed	326 participants	317 participants
		84.1; (80.3 to 88.0)	81.0; (76.8 to 85.1)
Week 16	Number Analyzed	321 participants	315 participants
		82.6; (78.5 to 86.6)	83.0; (78.9 to 87.0)
Week 20	Number Analyzed	320 participants	309 participants
		84.8; (80.9 to 88.6)	83.1; (79.1 to 87.2)
Week 24	Number Analyzed	295 participants	288 participants
		82.8; (78.6 to 86.9)	82.0; (77.6 to 86.4)
Week 28	Number Analyzed	292 participants	271 participants
		82.7; (78.5 to 86.8)	83.0; (78.7 to 87.4)
Week 32	Number Analyzed	287 participants	288 participants
		80.3; (75.9 to 84.7)	82.2; (77.8 to 86.5)
Week 36	Number Analyzed	293 participants	283 participants
		81.2; (76.8 to 85.6)	76.5; (71.7 to 81.3)
Week 40	Number Analyzed	286 participants	288 participants
		82.0; (77.6 to 86.3)	77.6; (72.9 to 82.3)
Week 44	Number Analyzed	285 participants	273 participants
		84.0; (79.8 to 88.2)	78.6; (73.9 to 83.2)
Week 48	Number Analyzed	282 participants	277 participants
		82.7; (78.3 to 87.1)	78.9; (74.1 to 83.6)
Week 52	Number Analyzed	283 participants	273 participants
		79.4; (74.8 to 84.0)	84.7; (80.5 to 88.9)
Week 56	Number Analyzed	283 participants	273 participants
		80.7; (76.1 to 85.2)	82.6; (78.2 to 87.0)
Week 60	Number Analyzed	278 participants	273 participants
		78.9; (74.2 to 83.6)	81.5; (77.0 to 86.0)
Week 64	Number Analyzed	276 participants	266 participants
		81.3; (76.8 to 85.8)	81.1; (76.5 to 85.7)
Week 68	Number Analyzed	276 participants	266 participants
		80.5; (76.0 to 85.1)	80.4; (75.8 to 85.0)
Week 72	Number Analyzed	276 participants	261 participants
		79.5; (74.8 to 84.1)	78.8; (74.0 to 83.6)
Week 76	Number Analyzed	268 participants	267 participants
		81.0; (76.4 to 85.6)	79.8; (75.2 to 84.5)
Week 80	Number Analyzed	275 participants	264 participants
		80.0; (75.3 to 84.7)	76.0; (71.0 to 81.1)
Week 84	Number Analyzed	279 participants	254 participants
		78.7; (73.9 to 83.5)	81.0; (76.3 to 85.7)
Week 88	Number Analyzed	276 participants	253 participants
		78.7; (73.9 to 83.5)	80.6; (75.9 to 85.4)
Week 92	Number Analyzed	273 participants	253 participants
		81.3; (76.7 to 85.8)	76.3; (71.2 to 81.4)
Week 96	Number Analyzed	266 participants	247 participants
		76.3; (71.3 to 81.3)	77.5; (72.5 to 82.6)
Week 100	Number Analyzed	272 participants	254 participants
		75.7; (70.8 to 80.7)	74.8; (69.6 to 80.0)
Week 104	Number Analyzed	263 participants	249 participants
		76.6; (71.6 to 81.6)	79.0; (74.0 to 84.0)
Week 108	Number Analyzed	267 participants	247 participants
		78.8; (74.0 to 83.6)	76.9; (71.7 to 82.1)
Week 112	Number Analyzed	267 participants	254 participants
		74.6; (69.5 to 79.8)	77.4; (72.3 to 82.5)

10. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 40, 44, and 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	302	291
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Avoiding a Loss of ≥15 Letters	95.8; (93.6 to 98.0)	97.3; (95.5 to 99.1)
Avoiding a Loss of ≥10 Letters	93.8; (91.1 to 96.4)	94.6; (92.2 to 97.1)
Avoiding a Loss of ≥5 Letters	91.2; (88.0 to 94.3)	88.5; (85.0 to 92.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Avoiding a Loss of ≥15 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -4.4 to 1.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants avoiding a loss of ≥15 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Avoiding a Loss of ≥10 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -4.5 to 2.8
	Estimation Comments	The treatment difference in CMH weighted percentage of participants avoiding a loss of ≥10 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Avoiding a Loss of ≥5 Letters: Treatment Difference at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -2.1 to 7.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants avoiding a loss of ≥5 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

11. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Averaged Over Weeks 52, 56, and 60
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 52, 56, and 60

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 52, 56, or 60 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	289	276
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	96.5; (94.4 to 98.6)	96.1; (94.0 to 98.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in CMH Weighted Percentages at Weeks 52-60
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -2.6 to 3.3
	Estimation Comments	The treatment difference in CMH weighted percentage of participants avoiding a loss of ≥15 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

12. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥15 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		99.4; (98.6 to 100.0)	98.1; (96.7 to 99.6)
Week 8	Number Analyzed	327 participants	322 participants
		98.5; (97.3 to 99.8)	97.8; (96.3 to 99.4)
Week 12	Number Analyzed	326 participants	317 participants
		98.5; (97.3 to 99.8)	98.1; (96.7 to 99.6)
Week 16	Number Analyzed	321 participants	315 participants
		97.6; (96.0 to 99.2)	98.4; (97.0 to 99.8)
Week 20	Number Analyzed	320 participants	309 participants
		97.3; (95.5 to 99.0)	98.4; (97.0 to 99.7)
Week 24	Number Analyzed	295 participants	288 participants
		96.6; (94.6 to 98.6)	97.2; (95.4 to 99.1)
Week 28	Number Analyzed	292 participants	271 participants
		97.0; (95.1 to 98.9)	97.8; (96.2 to 99.5)
Week 32	Number Analyzed	287 participants	288 participants
		97.0; (95.1 to 98.9)	96.9; (95.0 to 98.9)
Week 36	Number Analyzed	293 participants	283 participants
		97.0; (95.2 to 98.9)	96.5; (94.5 to 98.6)
Week 40	Number Analyzed	286 participants	288 participants
		96.2; (94.1 to 98.4)	97.6; (95.9 to 99.3)
Week 44	Number Analyzed	285 participants	273 participants
		95.9; (93.6 to 98.1)	96.4; (94.3 to 98.5)
Week 48	Number Analyzed	282 participants	277 participants
		95.8; (93.5 to 98.0)	96.9; (95.0 to 98.8)
Week 52	Number Analyzed	283 participants	273 participants
		94.9; (92.5 to 97.4)	96.8; (94.8 to 98.8)
Week 56	Number Analyzed	283 participants	273 participants
		96.1; (93.9 to 98.3)	96.8; (94.8 to 98.8)
Week 60	Number Analyzed	278 participants	273 participants
		95.0; (92.5 to 97.5)	96.1; (94.0 to 98.3)
Week 64	Number Analyzed	276 participants	266 participants
		96.4; (94.3 to 98.5)	94.9; (92.3 to 97.4)
Week 68	Number Analyzed	276 participants	266 participants
		94.7; (92.1 to 97.2)	96.0; (93.7 to 98.3)
Week 72	Number Analyzed	276 participants	261 participants
		94.5; (91.9 to 97.2)	95.4; (92.9 to 97.9)
Week 76	Number Analyzed	268 participants	267 participants
		94.9; (92.3 to 97.4)	93.7; (90.9 to 96.6)
Week 80	Number Analyzed	275 participants	264 participants
		93.9; (91.1 to 96.6)	93.3; (90.4 to 96.3)
Week 84	Number Analyzed	279 participants	254 participants
		92.5; (89.5 to 95.5)	93.8; (90.9 to 96.7)
Week 88	Number Analyzed	276 participants	253 participants
		94.1; (91.4 to 96.7)	94.3; (91.5 to 97.0)
Week 92	Number Analyzed	273 participants	253 participants
		93.0; (90.2 to 95.9)	94.6; (92.0 to 97.2)
Week 96	Number Analyzed	266 participants	247 participants
		92.6; (89.6 to 95.6)	95.0; (92.5 to 97.6)
Week 100	Number Analyzed	272 participants	254 participants
		92.5; (89.5 to 95.5)	93.9; (91.1 to 96.7)
Week 104	Number Analyzed	263 participants	249 participants
		92.9; (90.0 to 95.9)	94.0; (91.0 to 96.9)
Week 108	Number Analyzed	267 participants	247 participants
		92.3; (89.2 to 95.3)	93.3; (90.3 to 96.3)
Week 112	Number Analyzed	267 participants	254 participants
		91.8; (88.7 to 95.0)	93.0; (89.9 to 96.1)

13. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥10 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		98.5; (97.2 to 99.8)	96.2; (94.1 to 98.3)
Week 8	Number Analyzed	327 participants	322 participants
		97.0; (95.3 to 98.7)	96.9; (95.0 to 98.7)
Week 12	Number Analyzed	326 participants	317 participants
		97.0; (95.2 to 98.8)	96.8; (94.9 to 98.7)
Week 16	Number Analyzed	321 participants	315 participants
		96.6; (94.7 to 98.5)	96.8; (94.9 to 98.7)
Week 20	Number Analyzed	320 participants	309 participants
		95.2; (92.9 to 97.4)	96.1; (94.0 to 98.2)
Week 24	Number Analyzed	295 participants	288 participants
		95.2; (92.9 to 97.6)	95.5; (93.2 to 97.8)
Week 28	Number Analyzed	292 participants	271 participants
		95.0; (92.6 to 97.4)	95.2; (92.7 to 97.7)
Week 32	Number Analyzed	287 participants	288 participants
		94.6; (92.1 to 97.1)	95.9; (93.7 to 98.1)
Week 36	Number Analyzed	293 participants	283 participants
		95.3; (93.0 to 97.7)	94.4; (91.8 to 97.0)
Week 40	Number Analyzed	286 participants	288 participants
		93.8; (91.1 to 96.5)	94.6; (92.2 to 97.1)
Week 44	Number Analyzed	285 participants	273 participants
		94.1; (91.4 to 96.8)	92.1; (89.1 to 95.1)
Week 48	Number Analyzed	282 participants	277 participants
		92.2; (89.2 to 95.3)	94.8; (92.3 to 97.3)
Week 52	Number Analyzed	283 participants	273 participants
		91.4; (88.2 to 94.6)	93.8; (91.1 to 96.6)
Week 56	Number Analyzed	283 participants	273 participants
		93.3; (90.5 to 96.2)	95.0; (92.5 to 97.5)
Week 60	Number Analyzed	278 participants	273 participants
		91.4; (88.2 to 94.6)	93.2; (90.4 to 96.1)
Week 64	Number Analyzed	276 participants	266 participants
		93.5; (90.7 to 96.4)	92.3; (89.3 to 95.4)
Week 68	Number Analyzed	276 participants	266 participants
		91.9; (88.8 to 95.0)	92.9; (89.9 to 96.0)
Week 72	Number Analyzed	276 participants	261 participants
		92.4; (89.3 to 95.5)	91.6; (88.3 to 94.9)
Week 76	Number Analyzed	268 participants	267 participants
		93.1; (90.2 to 96.0)	90.1; (86.5 to 93.6)
Week 80	Number Analyzed	275 participants	264 participants
		92.1; (89.0 to 95.2)	89.9; (86.3 to 93.5)
Week 84	Number Analyzed	279 participants	254 participants
		90.3; (86.9 to 93.7)	91.8; (88.4 to 95.1)
Week 88	Number Analyzed	276 participants	253 participants
		90.8; (87.5 to 94.1)	92.3; (89.1 to 95.4)
Week 92	Number Analyzed	273 participants	253 participants
		90.7; (87.4 to 94.1)	91.0; (87.6 to 94.5)
Week 96	Number Analyzed	266 participants	247 participants
		90.4; (87.0 to 93.8)	92.6; (89.4 to 95.8)
Week 100	Number Analyzed	272 participants	254 participants
		90.7; (87.4 to 94.0)	91.6; (88.3 to 94.9)
Week 104	Number Analyzed	263 participants	249 participants
		89.0; (85.4 to 92.7)	92.2; (88.9 to 95.4)
Week 108	Number Analyzed	267 participants	247 participants
		88.5; (84.8 to 92.3)	91.2; (87.7 to 94.7)
Week 112	Number Analyzed	267 participants	254 participants
		88.5; (84.7 to 92.2)	89.5; (85.8 to 93.2)

14. Secondary Outcome

Title	Percentage of Participants Avoiding a Loss of ≥5 Letters From the Baseline BCVA in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted percentage of participants avoiding a loss of letters in BCVA from baseline was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		93.0; (90.4 to 95.6)	91.8; (88.9 to 94.7)
Week 8	Number Analyzed	327 participants	322 participants
		93.1; (90.4 to 95.7)	94.1; (91.5 to 96.6)
Week 12	Number Analyzed	326 participants	317 participants
		93.3; (90.7 to 95.9)	91.8; (88.8 to 94.7)
Week 16	Number Analyzed	321 participants	315 participants
		91.7; (88.7 to 94.6)	90.8; (87.7 to 94.0)
Week 20	Number Analyzed	320 participants	309 participants
		92.0; (89.1 to 94.9)	92.9; (90.0 to 95.7)
Week 24	Number Analyzed	295 participants	288 participants
		90.6; (87.4 to 93.9)	91.7; (88.6 to 94.8)
Week 28	Number Analyzed	292 participants	271 participants
		91.0; (87.9 to 94.1)	90.2; (86.7 to 93.7)
Week 32	Number Analyzed	287 participants	288 participants
		89.9; (86.5 to 93.2)	91.0; (87.7 to 94.3)
Week 36	Number Analyzed	293 participants	283 participants
		90.7; (87.5 to 94.0)	87.4; (83.6 to 91.2)
Week 40	Number Analyzed	286 participants	288 participants
		91.7; (88.6 to 94.9)	88.1; (84.5 to 91.7)
Week 44	Number Analyzed	285 participants	273 participants
		90.9; (87.7 to 94.2)	88.8; (85.3 to 92.3)
Week 48	Number Analyzed	282 participants	277 participants
		89.4; (85.9 to 93.0)	88.6; (85.0 to 92.2)
Week 52	Number Analyzed	283 participants	273 participants
		88.9; (85.3 to 92.5)	91.7; (88.6 to 94.8)
Week 56	Number Analyzed	283 participants	273 participants
		89.5; (86.0 to 93.0)	88.8; (85.2 to 92.5)
Week 60	Number Analyzed	278 participants	273 participants
		86.7; (82.9 to 90.6)	88.8; (85.2 to 92.4)
Week 64	Number Analyzed	276 participants	266 participants
		87.8; (84.1 to 91.6)	86.0; (82.0 to 90.1)
Week 68	Number Analyzed	276 participants	266 participants
		88.2; (84.5 to 91.9)	87.1; (83.2 to 91.0)
Week 72	Number Analyzed	276 participants	261 participants
		87.0; (83.1 to 90.9)	87.3; (83.4 to 91.2)
Week 76	Number Analyzed	268 participants	267 participants
		87.1; (83.2 to 91.1)	85.4; (81.2 to 89.5)
Week 80	Number Analyzed	275 participants	264 participants
		87.3; (83.5 to 91.2)	82.8; (78.3 to 87.3)
Week 84	Number Analyzed	279 participants	254 participants
		84.1; (79.9 to 88.4)	87.1; (83.1 to 91.2)
Week 88	Number Analyzed	276 participants	253 participants
		87.5; (83.7 to 91.3)	86.6; (82.5 to 90.6)
Week 92	Number Analyzed	273 participants	253 participants
		87.0; (83.1 to 90.9)	87.2; (83.2 to 91.2)
Week 96	Number Analyzed	266 participants	247 participants
		82.7; (78.4 to 87.1)	86.2; (82.1 to 90.4)
Week 100	Number Analyzed	272 participants	254 participants
		85.9; (81.9 to 89.8)	84.2; (79.9 to 88.5)
Week 104	Number Analyzed	263 participants	249 participants
		83.5; (79.1 to 87.8)	85.4; (81.1 to 89.7)
Week 108	Number Analyzed	267 participants	247 participants
		84.1; (79.9 to 88.4)	83.9; (79.4 to 88.5)
Week 112	Number Analyzed	267 participants	254 participants
		82.2; (77.7 to 86.7)	84.4; (80.0 to 88.8)

15. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 40, 44, and 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	302	291
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	24.5; (19.8 to 29.2)	26.2; (21.2 to 31.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in CMH Weighted Percentages at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -8.5 to 5.1
	Estimation Comments	The treatment difference in CMH weighted percentage of participants gaining ≥15 letters or achieving BCVA ≥84 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

16. Secondary Outcome

Title	Percentage of Participants Gaining ≥15 Letters From the Baseline BCVA or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		11.3; (7.9 to 14.6)	12.4; (8.9 to 15.9)
Week 8	Number Analyzed	327 participants	322 participants
		16.5; (12.5 to 20.4)	16.1; (12.2 to 20.0)
Week 12	Number Analyzed	326 participants	317 participants
		22.0; (17.7 to 26.4)	21.1; (16.7 to 25.4)
Week 16	Number Analyzed	321 participants	315 participants
		21.7; (17.4 to 26.1)	20.7; (16.2 to 25.1)
Week 20	Number Analyzed	320 participants	309 participants
		24.9; (20.2 to 29.5)	24.9; (20.2 to 29.6)
Week 24	Number Analyzed	295 participants	288 participants
		23.6; (18.9 to 28.3)	23.7; (18.9 to 28.6)
Week 28	Number Analyzed	292 participants	271 participants
		27.7; (22.7 to 32.7)	26.9; (21.8 to 32.1)
Week 32	Number Analyzed	287 participants	288 participants
		28.7; (23.6 to 33.8)	23.2; (18.4 to 27.9)
Week 36	Number Analyzed	293 participants	283 participants
		25.9; (21.1 to 30.7)	24.6; (19.7 to 29.5)
Week 40	Number Analyzed	286 participants	288 participants
		27.9; (22.9 to 32.9)	31.1; (25.9 to 36.4)
Week 44	Number Analyzed	285 participants	273 participants
		27.2; (22.2 to 32.1)	28.1; (22.8 to 33.3)
Week 48	Number Analyzed	282 participants	277 participants
		27.3; (22.3 to 32.4)	28.3; (23.1 to 33.6)
Week 52	Number Analyzed	283 participants	273 participants
		29.2; (24.1 to 34.3)	28.3; (23.1 to 33.5)
Week 56	Number Analyzed	283 participants	273 participants
		32.0; (26.7 to 37.2)	31.5; (26.1 to 36.9)
Week 60	Number Analyzed	278 participants	273 participants
		27.5; (22.5 to 32.5)	31.4; (26.0 to 36.8)
Week 64	Number Analyzed	276 participants	266 participants
		30.1; (25.0 to 35.3)	27.1; (21.9 to 32.3)
Week 68	Number Analyzed	276 participants	266 participants
		28.3; (23.1 to 33.4)	30.0; (24.6 to 35.3)
Week 72	Number Analyzed	276 participants	261 participants
		26.4; (21.4 to 31.4)	31.5; (26.0 to 36.9)
Week 76	Number Analyzed	268 participants	267 participants
		27.4; (22.2 to 32.5)	29.2; (23.9 to 34.4)
Week 80	Number Analyzed	275 participants	264 participants
		28.7; (23.4 to 34.0)	31.2; (25.7 to 36.6)
Week 84	Number Analyzed	279 participants	254 participants
		28.0; (22.8 to 33.1)	30.1; (24.6 to 35.5)
Week 88	Number Analyzed	276 participants	253 participants
		29.1; (23.8 to 34.4)	28.4; (23.2 to 33.6)
Week 92	Number Analyzed	273 participants	253 participants
		27.0; (21.8 to 32.1)	29.0; (23.6 to 34.3)
Week 96	Number Analyzed	266 participants	247 participants
		30.7; (25.3 to 36.0)	31.1; (25.5 to 36.6)
Week 100	Number Analyzed	272 participants	254 participants
		28.6; (23.3 to 33.9)	27.2; (22.0 to 32.5)
Week 104	Number Analyzed	263 participants	249 participants
		27.2; (22.0 to 32.4)	30.2; (24.8 to 35.6)
Week 108	Number Analyzed	267 participants	247 participants
		26.3; (21.1 to 31.4)	27.0; (21.7 to 32.4)
Week 112	Number Analyzed	267 participants	254 participants
		29.4; (24.1 to 34.7)	26.5; (21.4 to 31.6)

17. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 40, 44, and 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	302	291
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	55.2; (50.1 to 60.2)	49.4; (44.4 to 54.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in CMH Weighted Percentages at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; -1.4 to 12.9
	Estimation Comments	The treatment difference in CMH weighted percentage of participants achieving BCVA ≥69 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

18. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (<69 letters vs. ≥69 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		45.7; (41.1 to 50.2)	40.1; (35.8 to 44.5)
Week 8	Number Analyzed	327 participants	322 participants
		50.5; (45.8 to 55.1)	45.2; (40.7 to 49.7)
Week 12	Number Analyzed	326 participants	317 participants
		53.5; (48.8 to 58.3)	48.5; (43.8 to 53.3)
Week 16	Number Analyzed	321 participants	315 participants
		56.1; (51.2 to 60.9)	47.4; (42.8 to 52.1)
Week 20	Number Analyzed	320 participants	309 participants
		57.5; (52.6 to 62.4)	51.1; (46.3 to 55.9)
Week 24	Number Analyzed	295 participants	288 participants
		57.4; (52.4 to 62.4)	47.8; (42.9 to 52.8)
Week 28	Number Analyzed	292 participants	271 participants
		55.2; (50.0 to 60.4)	48.2; (43.2 to 53.2)
Week 32	Number Analyzed	287 participants	288 participants
		55.9; (50.8 to 61.1)	49.8; (45.0 to 54.6)
Week 36	Number Analyzed	293 participants	283 participants
		56.0; (50.9 to 61.0)	47.4; (42.2 to 52.6)
Week 40	Number Analyzed	286 participants	288 participants
		54.7; (49.5 to 59.9)	52.7; (47.5 to 57.9)
Week 44	Number Analyzed	285 participants	273 participants
		56.3; (51.4 to 61.3)	52.5; (47.3 to 57.7)
Week 48	Number Analyzed	282 participants	277 participants
		55.0; (49.8 to 60.2)	52.3; (47.1 to 57.5)
Week 52	Number Analyzed	283 participants	273 participants
		55.9; (50.6 to 61.1)	55.6; (50.4 to 60.9)
Week 56	Number Analyzed	283 participants	273 participants
		57.1; (51.8 to 62.3)	52.9; (47.7 to 58.2)
Week 60	Number Analyzed	278 participants	273 participants
		53.0; (47.6 to 58.3)	53.6; (48.3 to 58.9)
Week 64	Number Analyzed	276 participants	266 participants
		58.8; (53.5 to 64.2)	52.9; (47.5 to 58.3)
Week 68	Number Analyzed	276 participants	266 participants
		57.0; (51.7 to 62.4)	55.5; (50.0 to 60.9)
Week 72	Number Analyzed	276 participants	261 participants
		58.1; (52.7 to 63.4)	53.3; (48.0 to 58.6)
Week 76	Number Analyzed	268 participants	267 participants
		58.0; (52.6 to 63.4)	54.0; (48.6 to 59.3)
Week 80	Number Analyzed	275 participants	264 participants
		57.3; (52.0 to 62.6)	51.9; (46.5 to 57.4)
Week 84	Number Analyzed	279 participants	254 participants
		58.4; (53.1 to 63.7)	56.9; (51.5 to 62.4)
Week 88	Number Analyzed	276 participants	253 participants
		57.2; (51.9 to 62.6)	51.1; (45.6 to 56.5)
Week 92	Number Analyzed	273 participants	253 participants
		56.1; (50.8 to 61.4)	54.9; (49.5 to 60.3)
Week 96	Number Analyzed	266 participants	247 participants
		55.5; (49.9 to 61.0)	53.9; (48.4 to 59.4)
Week 100	Number Analyzed	272 participants	254 participants
		55.1; (49.5 to 60.7)	51.7; (46.2 to 57.2)
Week 104	Number Analyzed	263 participants	249 participants
		55.1; (49.4 to 60.7)	52.8; (47.3 to 58.2)
Week 108	Number Analyzed	267 participants	247 participants
		54.8; (49.1 to 60.4)	51.0; (45.5 to 56.5)
Week 112	Number Analyzed	267 participants	254 participants
		55.7; (50.2 to 61.1)	51.0; (45.6 to 56.4)

19. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, average of Weeks 40, 44, and 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Participants with at least one non-missing, valid assessment at Weeks 40, 44, or 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	302	291
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	7.9; (5.0 to 10.8)	7.5; (4.7 to 10.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in CMH Weighted Percentages at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in CMH Weighted Percentage
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -3.6 to 4.4
	Estimation Comments	The treatment difference in CMH weighted percentage of participants with BCVA ≤38 letters is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept.

20. Secondary Outcome

Title	Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time
Description	Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	328 participants	323 participants
		6.8; (4.3 to 9.4)	6.1; (3.7 to 8.5)
Week 8	Number Analyzed	327 participants	322 participants
		7.4; (4.8 to 10.1)	6.2; (3.7 to 8.6)
Week 12	Number Analyzed	326 participants	317 participants
		7.6; (5.0 to 10.2)	5.9; (3.5 to 8.3)
Week 16	Number Analyzed	321 participants	315 participants
		9.5; (6.6 to 12.5)	5.3; (3.0 to 7.6)
Week 20	Number Analyzed	320 participants	309 participants
		9.3; (6.4 to 12.3)	5.7; (3.3 to 8.1)
Week 24	Number Analyzed	295 participants	288 participants
		8.1; (5.2 to 11.1)	6.3; (3.7 to 8.9)
Week 28	Number Analyzed	292 participants	271 participants
		7.4; (4.6 to 10.3)	6.4; (3.7 to 9.1)
Week 32	Number Analyzed	287 participants	288 participants
		8.1; (5.1 to 11.0)	6.6; (4.0 to 9.2)
Week 36	Number Analyzed	293 participants	283 participants
		7.8; (4.9 to 10.6)	6.8; (4.1 to 9.5)
Week 40	Number Analyzed	286 participants	288 participants
		8.3; (5.3 to 11.3)	7.6; (4.8 to 10.3)
Week 44	Number Analyzed	285 participants	273 participants
		7.9; (4.9 to 10.9)	6.8; (4.0 to 9.5)
Week 48	Number Analyzed	282 participants	277 participants
		9.7; (6.5 to 12.9)	6.3; (3.6 to 9.0)
Week 52	Number Analyzed	283 participants	273 participants
		9.1; (6.0 to 12.2)	6.5; (3.7 to 9.2)
Week 56	Number Analyzed	283 participants	273 participants
		8.1; (5.1 to 11.1)	6.3; (3.6 to 9.0)
Week 60	Number Analyzed	278 participants	273 participants
		8.2; (5.2 to 11.3)	7.3; (4.5 to 10.2)
Week 64	Number Analyzed	276 participants	266 participants
		7.1; (4.2 to 10.1)	7.2; (4.3 to 10.1)
Week 68	Number Analyzed	276 participants	266 participants
		8.8; (5.6 to 12.0)	6.8; (4.0 to 9.6)
Week 72	Number Analyzed	276 participants	261 participants
		8.4; (5.2 to 11.6)	6.2; (3.4 to 8.9)
Week 76	Number Analyzed	268 participants	267 participants
		9.5; (6.2 to 12.9)	7.4; (4.5 to 10.3)
Week 80	Number Analyzed	275 participants	264 participants
		9.8; (6.5 to 13.1)	8.4; (5.3 to 11.5)
Week 84	Number Analyzed	279 participants	254 participants
		9.3; (6.0 to 12.6)	7.2; (4.2 to 10.1)
Week 88	Number Analyzed	276 participants	253 participants
		8.4; (5.2 to 11.6)	7.5; (4.5 to 10.4)
Week 92	Number Analyzed	273 participants	253 participants
		8.9; (5.6 to 12.2)	9.0; (5.8 to 12.2)
Week 96	Number Analyzed	266 participants	247 participants
		10.4; (6.8 to 13.9)	9.7; (6.5 to 13.0)
Week 100	Number Analyzed	272 participants	254 participants
		10.3; (6.8 to 13.8)	10.9; (7.5 to 14.4)
Week 104	Number Analyzed	263 participants	249 participants
		9.2; (5.8 to 12.6)	9.8; (6.4 to 13.1)
Week 108	Number Analyzed	267 participants	247 participants
		9.5; (6.0 to 12.9)	10.0; (6.5 to 13.4)
Week 112	Number Analyzed	267 participants	254 participants
		9.0; (5.7 to 12.4)	10.6; (7.1 to 14.0)

21. Secondary Outcome

Title	Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 48
Description	Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 48. The treatment interval at a given visit is defined as the treatment interval decision followed at that visit. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

The analysis included all participants randomized to the faricimab arm who completed their Week 48 visit.

Arm/Group Title	Arm A: Faricimab
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
Overall Number of Participants Analyzed	316
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Once Every 8 Weeks	22.2; (17.6 to 26.7)
Once Every 12 Weeks	32.9; (27.7 to 38.1)
Once Every 16 Weeks	44.9; (39.4 to 50.4)

22. Secondary Outcome

Title	Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 60
Description	Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 60. The treatment interval at a given visit is defined as the treatment interval decision followed at that visit. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Week 60

Outcome Measure Data

Analysis Population Description

The analysis included all participants randomized to the faricimab arm who completed their Week 60 visit.

Arm/Group Title	Arm A: Faricimab
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
Overall Number of Participants Analyzed	305
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Once Every 8 Weeks	21.6; (17.0 to 26.3)
Once Every 12 Weeks	32.8; (27.5 to 38.1)
Once Every 16 Weeks	45.6; (40.0 to 51.2)

23. Secondary Outcome

Title	Percentage of Participants in the Faricimab Arm on Once Every 8-Weeks, 12-Weeks, or 16-Weeks Treatment Intervals Among Those Completing Week 112
Description	Percentages are based on the number of participants randomized to the faricimab arm who have not discontinued the study at Week 112. Treatment interval at a given visit is defined as the treatment interval decision followed at that visit. Treatment interval at Week 112 is calculated using data recorded at Week 108. The 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Weeks 108 and 112

Outcome Measure Data

Analysis Population Description

The analysis included all participants randomized to the faricimab arm who completed their Week 112 visit.

Arm/Group Title	Arm A: Faricimab
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
Overall Number of Participants Analyzed	287
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Once Every 8 Weeks	18.8; (14.3 to 23.3)
Once Every 12 Weeks	14.3; (10.2 to 18.3)
Once Every 16 Weeks	66.9; (61.4 to 72.4)

24. Secondary Outcome

Title	Number of Study Drug Injections Received in the Study Eye Through Week 48
Description	[Not Specified]
Time Frame	From Baseline through Week 48

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Median (Full Range); Unit of Measure: Injections
	6.0; (1 to 8)	8.0; (1 to 8)

25. Secondary Outcome

Title	Number of Study Drug Injections Received in the Study Eye Through Week 60
Description	[Not Specified]
Time Frame	From Baseline through Week 60

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Median (Full Range); Unit of Measure: Injections
	7.0; (1 to 10)	9.0; (1 to 9)

26. Secondary Outcome

Title	Number of Study Drug Injections Received in the Study Eye Through Week 108
Description	[Not Specified]
Time Frame	From Baseline through Week 108

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Median (Full Range); Unit of Measure: Injections
	10.0; (1 to 16)	15.0; (1 to 15)

27. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 40, 44, and 48
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group iteraction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	From Baseline through Week 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: microns
	-137.1; (-143.1 to -131.2)	-130.8; (-136.8 to -124.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in Adjusted Means at Weeks 40-48
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) 95%; -14.8 to 2.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.30
	Estimation Comments	The treatment difference in adjusted means of change from baseline CST is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept. MMRM adjustments are listed in the outcome measure description.

28. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 52, 56, and 60
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	From Baseline through Week 60

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: microns
	-135.7; (-141.2 to -130.1)	-137.0; (-142.7 to -131.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Faricimab, Arm B: Aflibercept
	Comments	Treatment Difference in Adjusted Means at Weeks 52-60
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -6.6 to 9.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.05
	Estimation Comments	The treatment difference in adjusted means of change from baseline CST is the calculated difference of Arm A: Faricimab and Arm B: Aflibercept. MMRM adjustments are listed in the outcome measure description.

29. Secondary Outcome

Title	Change From Baseline in Central Subfield Thickness in the Study Eye Over Time
Description	Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. For the Mixed Model of Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (<33 letters and ≥33 letters), and region (U.S. and Canada, Asia, and the rest of the world). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	327
Mean (95% Confidence Interval); Unit of Measure: microns
Week 4	-126.5; (-132.3 to -120.6)	-113.9; (-119.8 to -108.0)
Week 8	-138.0; (-143.7 to -132.3)	-123.8; (-129.6 to -118.0)
Week 12	-141.7; (-147.1 to -136.3)	-129.6; (-135.0 to -124.1)
Week 16	-143.7; (-150.3 to -137.1)	-112.9; (-119.6 to -106.2)
Week 20	-130.9; (-136.8 to -125.0)	-132.9; (-138.8 to -126.9)
Week 24	-130.1; (-137.1 to -123.1)	-112.2; (-119.3 to -105.2)
Week 28	-127.3; (-134.0 to -120.6)	-130.1; (-136.9 to -123.3)
Week 32	-138.6; (-145.8 to -131.5)	-115.3; (-122.5 to -108.1)
Week 36	-124.6; (-131.3 to -118.0)	-135.2; (-141.9 to -128.5)
Week 40	-142.5; (-149.3 to -135.6)	-122.5; (-129.4 to -115.6)
Week 44	-130.9; (-136.7 to -125.1)	-141.6; (-147.6 to -135.7)
Week 48	-135.5; (-142.3 to -128.6)	-123.9; (-130.8 to -117.0)
Week 52	-140.9; (-146.4 to -135.3)	-139.6; (-145.3 to -134.0)
Week 56	-138.9; (-145.7 to -132.1)	-125.6; (-132.5 to -118.6)
Week 60	-125.9; (-132.0 to -119.7)	-142.3; (-148.6 to -136.1)
Week 64	-143.8; (-150.3 to -137.2)	-126.0; (-132.7 to -119.3)
Week 68	-138.0; (-143.9 to -132.2)	-138.8; (-144.8 to -132.8)
Week 72	-140.7; (-147.3 to -134.1)	-128.8; (-135.5 to -122.0)
Week 76	-136.1; (-142.4 to -129.7)	-139.0; (-145.4 to -132.6)
Week 80	-144.4; (-151.1 to -137.8)	-128.7; (-135.5 to -121.9)
Week 84	-143.5; (-149.2 to -137.8)	-143.2; (-149.1 to -137.4)
Week 88	-145.5; (-151.6 to -139.5)	-133.3; (-139.5 to -127.1)
Week 92	-142.1; (-148.0 to -136.1)	-143.2; (-149.3 to -137.1)
Week 96	-146.8; (-153.1 to -140.4)	-134.7; (-141.2 to -128.2)
Week 100	-145.0; (-151.7 to -138.3)	-146.2; (-153.1 to -139.3)
Week 104	-149.6; (-156.3 to -142.8)	-137.4; (-144.3 to -130.5)
Week 108	-148.5; (-154.4 to -142.6)	-148.3; (-154.4 to -142.2)
Week 112	-152.9; (-159.2 to -146.7)	-139.1; (-145.5 to -132.7)

30. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time
Description	Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 millimetre [mm]). The weighted estimates of the percentage of participants with absence of intraretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	324 participants	320 participants
		86.9; (83.5 to 90.4)	82.9; (78.9 to 87.0)
Week 8	Number Analyzed	324 participants	316 participants
		88.5; (85.2 to 91.9)	84.6; (80.7 to 88.5)
Week 12	Number Analyzed	323 participants	315 participants
		87.5; (84.0 to 91.0)	84.5; (80.6 to 88.5)
Week 16	Number Analyzed	320 participants	314 participants
		90.6; (87.5 to 93.7)	76.5; (71.9 to 81.0)
Week 20	Number Analyzed	320 participants	305 participants
		78.8; (74.5 to 83.0)	86.1; (82.3 to 89.8)
Week 24	Number Analyzed	294 participants	284 participants
		78.7; (74.2 to 83.1)	78.0; (73.4 to 82.7)
Week 28	Number Analyzed	291 participants	273 participants
		77.1; (72.4 to 81.8)	85.9; (81.8 to 89.9)
Week 32	Number Analyzed	286 participants	291 participants
		86.3; (82.5 to 90.2)	78.3; (73.6 to 82.9)
Week 36	Number Analyzed	293 participants	278 participants
		79.6; (75.0 to 84.1)	86.1; (82.1 to 90.1)
Week 40	Number Analyzed	277 participants	278 participants
		84.5; (80.3 to 88.7)	77.5; (72.7 to 82.3)
Week 44	Number Analyzed	275 participants	258 participants
		78.5; (73.7 to 83.2)	84.2; (79.9 to 88.5)
Week 48	Number Analyzed	274 participants	269 participants
		84.1; (79.8 to 88.4)	77.7; (72.8 to 82.5)
Week 52	Number Analyzed	281 participants	270 participants
		85.9; (81.9 to 89.8)	85.3; (81.1 to 89.4)
Week 56	Number Analyzed	281 participants	272 participants
		85.2; (81.1 to 89.2)	81.1; (76.6 to 85.6)
Week 60	Number Analyzed	273 participants	266 participants
		77.8; (73.0 to 82.6)	85.4; (81.2 to 89.5)
Week 104	Number Analyzed	259 participants	247 participants
		86.0; (81.9 to 90.1)	80.0; (75.1 to 84.9)
Week 108	Number Analyzed	264 participants	243 participants
		82.2; (77.7 to 86.6)	83.5; (79.0 to 88.1)
Week 112	Number Analyzed	266 participants	251 participants
		85.9; (81.8 to 90.0)	80.5; (75.7 to 85.4)

31. Secondary Outcome

Title	Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time
Description	Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of subretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	327 participants	319 participants
		70.9; (66.1 to 75.7)	61.7; (56.4 to 66.9)
Week 8	Number Analyzed	323 participants	319 participants
		79.8; (75.6 to 84.1)	73.6; (68.9 to 78.4)
Week 12	Number Analyzed	324 participants	315 participants
		88.6; (85.1 to 92.0)	79.6; (75.3 to 84.0)
Week 16	Number Analyzed	320 participants	315 participants
		90.6; (87.4 to 93.8)	63.8; (58.6 to 68.9)
Week 20	Number Analyzed	320 participants	308 participants
		76.1; (71.6 to 80.7)	80.4; (76.1 to 84.8)
Week 24	Number Analyzed	295 participants	287 participants
		73.7; (68.8 to 78.5)	59.1; (53.5 to 64.6)
Week 28	Number Analyzed	292 participants	272 participants
		71.5; (66.6 to 76.4)	78.7; (73.9 to 83.5)
Week 32	Number Analyzed	287 participants	291 participants
		82.6; (78.3 to 87.0)	62.2; (56.7 to 67.7)
Week 36	Number Analyzed	293 participants	282 participants
		70.6; (65.5 to 75.7)	80.7; (76.1 to 85.2)
Week 40	Number Analyzed	283 participants	285 participants
		77.6; (72.9 to 82.3)	63.9; (58.4 to 69.5)
Week 44	Number Analyzed	280 participants	269 participants
		65.7; (60.3 to 71.0)	76.2; (71.1 to 81.2)
Week 48	Number Analyzed	278 participants	274 participants
		72.5; (67.5 to 77.5)	62.1; (56.5 to 67.7)
Week 52	Number Analyzed	281 participants	271 participants
		83.0; (78.8 to 87.3)	80.6; (76.0 to 85.3)
Week 56	Number Analyzed	282 participants	271 participants
		80.7; (76.3 to 85.2)	71.6; (66.4 to 76.8)
Week 60	Number Analyzed	278 participants	271 participants
		63.6; (58.1 to 69.0)	80.0; (75.3 to 84.8)
Week 104	Number Analyzed	262 participants	248 participants
		80.0; (75.3 to 84.7)	73.9; (68.5 to 79.3)
Week 108	Number Analyzed	266 participants	244 participants
		76.1; (71.2 to 81.0)	80.7; (75.8 to 85.5)
Week 112	Number Analyzed	267 participants	252 participants
		80.9; (76.4 to 85.4)	77.5; (72.4 to 82.6)

32. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time
Description	Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of intraretinal and subretinal fluid were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	324 participants	319 participants
		59.5; (54.2 to 64.8)	49.8; (44.4 to 55.2)
Week 8	Number Analyzed	323 participants	315 participants
		70.2; (65.2 to 75.1)	61.6; (56.3 to 66.9)
Week 12	Number Analyzed	323 participants	315 participants
		77.0; (72.4 to 81.5)	66.6; (61.5 to 71.7)
Week 16	Number Analyzed	319 participants	315 participants
		82.4; (78.3 to 86.5)	47.6; (42.2 to 53.0)
Week 20	Number Analyzed	320 participants	305 participants
		62.3; (57.3 to 67.4)	68.6; (63.6 to 73.7)
Week 24	Number Analyzed	295 participants	284 participants
		56.5; (50.8 to 62.1)	45.4; (39.7 to 51.1)
Week 28	Number Analyzed	291 participants	273 participants
		55.5; (49.9 to 61.1)	66.5; (61.0 to 72.0)
Week 32	Number Analyzed	286 participants	291 participants
		73.1; (68.0 to 78.1)	48.6; (42.9 to 54.3)
Week 36	Number Analyzed	293 participants	278 participants
		56.3; (50.8 to 61.9)	68.3; (62.9 to 73.7)
Week 40	Number Analyzed	278 participants	281 participants
		65.8; (60.3 to 71.2)	49.0; (43.2 to 54.8)
Week 44	Number Analyzed	277 participants	262 participants
		49.5; (43.7 to 55.3)	64.3; (58.5 to 70.0)
Week 48	Number Analyzed	277 participants	270 participants
		62.2; (56.6 to 67.8)	46.1; (40.3 to 52.0)
Week 52	Number Analyzed	281 participants	270 participants
		70.3; (65.2 to 75.5)	68.8; (63.4 to 74.3)
Week 56	Number Analyzed	281 participants	272 participants
		66.9; (61.5 to 72.3)	57.5; (51.8 to 63.3)
Week 60	Number Analyzed	275 participants	266 participants
		49.3; (43.5 to 55.0)	69.1; (63.6 to 74.6)
Week 104	Number Analyzed	259 participants	247 participants
		68.1; (62.5 to 73.7)	58.6; (52.7 to 64.6)
Week 108	Number Analyzed	264 participants	243 participants
		61.6; (55.9 to 67.3)	67.1; (61.3 to 72.9)
Week 112	Number Analyzed	266 participants	251 participants
		68.7; (63.3 to 74.1)	61.1; (55.1 to 67.1)

33. Secondary Outcome

Title	Percentage of Participants With Absence of Pigment Epithelial Detachment in the Study Eye Over Time
Description	Pigment epithelial detachment was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants with absence of pigment epithelial detachment were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥74 letters, 73-55 letters, and ≤54 letters), baseline LLD (≥33 letters and <33 letters), and region (U.S. and Canada vs. rest of the world). Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.03% CI.
Time Frame	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 104, 108, and 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. At a given timepoint, the number analyzed includes participants with a non-missing, valid assessment at that timepoint.

Arm/Group Title		Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed		331	327
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 4	Number Analyzed	323 participants	320 participants
		3.7; (1.7 to 5.8)	5.6; (3.1 to 8.1)
Week 8	Number Analyzed	321 participants	318 participants
		3.1; (1.3 to 5.0)	4.1; (1.9 to 6.2)
Week 12	Number Analyzed	321 participants	314 participants
		4.7; (2.4 to 7.0)	5.5; (3.0 to 8.0)
Week 16	Number Analyzed	316 participants	313 participants
		2.5; (0.8 to 4.1)	5.8; (3.2 to 8.4)
Week 20	Number Analyzed	316 participants	306 participants
		3.8; (1.7 to 5.9)	6.0; (3.4 to 8.6)
Week 24	Number Analyzed	293 participants	284 participants
		4.1; (1.8 to 6.3)	4.9; (2.5 to 7.4)
Week 28	Number Analyzed	292 participants	273 participants
		2.6; (0.9 to 4.4)	1.9; (0.3 to 3.5)
Week 32	Number Analyzed	287 participants	291 participants
		4.3; (2.0 to 6.6)	1.8; (0.3 to 3.3)
Week 36	Number Analyzed	293 participants	283 participants
		4.8; (2.4 to 7.1)	3.9; (1.7 to 6.1)
Week 40	Number Analyzed	284 participants	286 participants
		6.3; (3.5 to 9.0)	7.3; (4.4 to 10.3)
Week 44	Number Analyzed	282 participants	270 participants
		3.9; (1.7 to 6.2)	9.1; (5.9 to 12.4)
Week 48	Number Analyzed	280 participants	275 participants
		3.3; (1.2 to 5.3)	6.5; (3.7 to 9.3)
Week 52	Number Analyzed	273 participants	267 participants
		5.8; (3.1 to 8.5)	8.1; (5.0 to 11.3)
Week 56	Number Analyzed	272 participants	266 participants
		4.7; (2.3 to 7.2)	5.2; (2.7 to 7.7)
Week 60	Number Analyzed	278 participants	271 participants
		3.5; (1.4 to 5.6)	6.3; (3.4 to 9.1)
Week 104	Number Analyzed	260 participants	246 participants
		8.0; (4.8 to 11.2)	8.3; (5.0 to 11.7)
Week 108	Number Analyzed	264 participants	244 participants
		6.9; (3.9 to 10.0)	8.0; (4.7 to 11.2)
Week 112	Number Analyzed	264 participants	248 participants
		8.1; (4.9 to 11.3)	12.5; (8.4 to 16.5)

34. Secondary Outcome

Title	Percentage of Participants With Absence of Intraretinal Cysts in the Study Eye Over Time
Description	[Not Specified]
Time Frame	Up to 112 weeks

Outcome Measure Data

Analysis Population Description

The percentage of participants with absence of intraretinal cysts over time was planned but it was not evaluated (i.e., 0 participants analyzed) because the absence of intraretinal fluid and the absence of intraretinal cysts are described by the same variable during reading center grading.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

35. Secondary Outcome

Title	Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 48
Description	The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and Week 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	240	236
Mean (Standard Deviation); Unit of Measure: millimetres squared (mm^2)
	0.3 (4.6)	1.1 (4.4)

36. Secondary Outcome

Title	Change From Baseline in Total Area of Choroidal Neovascularization Lesion in the Study Eye at Week 112
Description	The total area of the choroidal neovascularization lesion in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Time Frame	Baseline and Week 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and Week 112 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	240	224
Mean (Standard Deviation); Unit of Measure: millimetres squared (mm^2)
	1.7 (7.5)	1.7 (4.2)

37. Secondary Outcome

Title	Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 48
Description	The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and Week 48 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	241	238
Mean (Standard Deviation); Unit of Measure: millimetres squared (mm^2)
	-3.3 (6.6)	-2.1 (6.3)

38. Secondary Outcome

Title	Change From Baseline in Total Area of Choroidal Neovascularization Leakage in the Study Eye at Week 112
Description	The total area of choroidal neovascularization leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). Assessments were censored following COVID-19 related intercurrent events. Baseline was defined as the last available measurement obtained on or prior to randomization.
Time Frame	Baseline and Week 112

Outcome Measure Data

Analysis Population Description

ITT Population: all participants who were randomized in the study, grouped according to the treatment assigned at randomization. Only participants with non-missing, valid assessments at Baseline and Week 112 were included in this analysis.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	239	220
Mean (Standard Deviation); Unit of Measure: millimetres squared (mm^2)
	-5.3 (7.2)	-4.2 (5.9)

39. Secondary Outcome

Title	Percentage of Participants With at Least One Adverse Event
Description	This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Time Frame	From first dose of study drug through end of study (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Measure Type: Number; Unit of Measure: Percentage of participants
Adverse Event (AE)	84.9	88.0
Serious AE (SAE)	27.5	31.0
AE Leading to Withdrawal from Study Treatment	4.8	2.8
AE of Special Interest (AESI)	7.3	6.1

40. Secondary Outcome

Title	Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye
Description	This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Time Frame	From first dose of study drug through end of study (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Measure Type: Number; Unit of Measure: Percentage of participants
Study Eye: Adverse Event (AE)	52.9	47.5
Study Eye: Serious AE (SAE)	4.5	4.9
Study Eye: AE Leading to Withdrawal from Treatment	3.3	1.8
Study Eye: Treatment-related AE	3.6	3.1
Study Eye: Treatment-related SAE	1.8	0.6
Study Eye: AE of Special Interest (AESI)	3.9	4.3
Study Eye: AESI, Drop in VA Score ≥30 Letters	2.7	3.1
Study Eye: AESI, Associated with Severe IOI	0.6	0.3
Study Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	0.6	0.9
Study Eye: Suspected Transmission of Infectious Agent by Study Drug	0.0	0.3
Fellow Eye: AE	46.2	41.7
Fellow Eye: SAE	3.6	2.5
Fellow Eye: AESI	3.0	2.1
Fellow Eye: AESI, Drop in VA Score ≥30 Letters	2.1	1.8
Fellow Eye: AESI, Intervention Req. to Prevent Permanent Vision Loss	0.9	0.3

41. Secondary Outcome

Title	Percentage of Participants With at Least One Non-Ocular Adverse Event
Description	This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Time Frame	From first dose of study drug through end of study (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

Safety Evaluable Population: all participants who received at least one dose of active study drug (faricimab or aflibercept) in the study eye.

Arm/Group Title	Arm A: Faricimab	Arm B: Aflibercept
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).	Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
Overall Number of Participants Analyzed	331	326
Measure Type: Number; Unit of Measure: Percentage of participants
Adverse Event (AE)	71.0	75.8
Serious AE (SAE)	21.8	26.4
AE Leading to Withdrawal from Study Treatment	1.5	0.9
AE of Special Interest (AESI)	0.3	0.0

42. Secondary Outcome

Title	Plasma Concentration of Faricimab Over Time
Description	Faricimab concentration in plasma was determined using a validated immunoassay method.
Time Frame	Pre-dose at Baseline, Weeks 4, 16, 20, 48, 76, and 112

Outcome Measure Data

Analysis Population Description

This analysis only includes Arm A participants who received treatment with faricimab in the pharmacokinetic-evaluable population, which includes safety-evaluable participants with at least one plasma sample, provided sufficient dosing information (dose and dosing time) was available. The number of participants analyzed at a given timepoint includes those with an available plasma sample and dosing information at that timepoint.

Arm/Group Title		Arm A: Faricimab
Arm/Group Description:		Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
Overall Number of Participants Analyzed		331
Mean (Standard Deviation); Unit of Measure: micrograms per millilitre (μg/mL)
Baseline	Number Analyzed	321 participants
		0.0000 (0.0001)
Week 4	Number Analyzed	319 participants
		0.0287 (0.0209)
Week 16	Number Analyzed	300 participants
		0.0333 (0.0250)
Week 20	Number Analyzed	305 participants
		0.0046 (0.0051)
Week 48	Number Analyzed	273 participants
		0.0149 (0.0185)
Week 76	Number Analyzed	269 participants
		0.0053 (0.0117)
Week 112	Number Analyzed	278 participants
		0.0119 (0.0149)

43. Secondary Outcome

Title	Percentage of Participants Who Tested Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study
Description	Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.
Time Frame	Pre-dose at Baseline, Weeks 4, 20, 48, 76, and 112

Outcome Measure Data

Analysis Population Description

The immunogenicity-analysis population includes all participants randomized to the faricimab arm with at least one determinant ADA assessment. Only those with at least one post-baseline ADA assessment were included in this analysis.

Arm/Group Title	Arm A: Faricimab
Arm/Group Description:	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).
Overall Number of Participants Analyzed	330
Measure Type: Number; Unit of Measure: Percentage of participants
Total Treatment-Emergent ADA-Positive	16.1
Treatment-Induced ADA-Positive	16.1
Treatment-Boosted ADA-Positive	0.0

Adverse Events

Time Frame	From first dose of study drug through end of study (up to 112 weeks)
Adverse Event Reporting Description	Adverse events (AEs) are reported for the safety population, which includes all participants who received at least one injection of active study drug (faricimab or aflibercept) in the study eye. For ocular AEs, the number of participants and events reported per term are combined totals of AEs that occurred in the study eye or the fellow eye.
Arm/Group Title	Arm A: Faricimab		Arm B: Aflibercept
Arm/Group Description	Participants randomized to Arm A received 6 mg of faricimab intravitreally (IVT) once every 4 weeks (Q4W) up to Week 12 (4 injections). At Week 20, protocol-defined assessment of disease activity required Arm A participants with active disease to be treated with a once every 8 weeks (Q8W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 20, 28, 36, 44, 52, and 60). A second protocol-defined assessment of disease activity at Week 24 required Arm A participants with active disease (excluding those with active disease at Week 20) to be treated with a once every 12 weeks (Q12W) dosing regimen of 6 mg of faricimab IVT (i.e., injections at Weeks 24, 36, 48, and 60). Participants receiving faricimab who did not have active disease according to the protocol-defined criteria at Week 20 and Week 24 were treated with 6 mg of faricimab IVT once every 16 weeks (Q16W) (i.e., injections at Weeks 28, 44, and 60). From Week 60 (when all Arm A participants were scheduled to receive study drug) to Week 108, Arm A participants were to be treated according to a personalized treatment interval (PTI) dosing regimen (Q8W, Q12W, or Q16W).		Participants randomized to the active comparator (Arm B) received a 2-mg dose of aflibercept that was administered intravitreally (IVT) Q8W, after 3 consecutive monthly doses during the 108-week treatment period. Participants were to receive 15 IVT injections of aflibercept during the 108-week treatment period comprising three initiating injections (2 mg of aflibercept Q4W to Week 8), followed by 12 maintenance injections (2 mg of aflibercept Q8W at Weeks 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, and 104).
All-Cause Mortality
	Arm A: Faricimab