An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia

• Percent reduction of low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), total cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) at various timepoints [ Time Frame: Through up to four years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: No ]
  

• Effects of mipomersen (ISIS 301012) on triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1 (apoA-1), lipoprotein (a) (Lp(a), lipoprotein sub-classes and high-sensitivity C-Reactive Protein [ Time Frame: Through up to four years of treatment and 24 weeks of follow-up ] [ Designated as safety issue: No ]
  

All familial hypercholesterolemia (FH) or severe hypercholesterolemia patients who have tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7 (NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to Week 28 are eligible for participation in this open label treatment extension study for up to 4 years or until mipomersen is commercially available, whichever comes first. Consenting patients who have tolerated mipomersen and satisfactorily completed 301012-CS17 (NCT00477594) through Year 3 may also enroll for up to an additional 2 years of treatment in this study or until mipomersen is commercially available, whichever comes first. All patients who enter the study will receive 200 mg mipomersen (ISIS 301012) subcutaneously (s.c.) every week, including those who were randomized to placebo in their initial study. Patients who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weigh < 50 kg will receive 160 mg every week. Dose adjustments (70 mg injections administered three times per week, on separate days) are allowed for patients who are not tolerating or who have had previous issues with tolerating the once a week injections due to injection site reactions (ISRs) or flu-like symptoms. Study visits and clinical lab assessments including hematology with differential, chemistry, serum lipid panel (total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), apoA-1, triglycerides (TG) and Lp(a), and urinalysis will be performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS 301012) levels will be measured to estimate exposure. Subjects who complete dosing or who discontinue prematurely from the study for any reason will be followed for safety for 24 weeks (safety follow-up period) after their last dose of mipomersen (ISIS 301012) or longer in the case of a significant adverse events (AE) or abnormal biochemical or clinical finding. Subjects will be required to return to the study center for clinical evaluation and clinical laboratory tests every 8 weeks during the safety follow-up period.