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

All familial hypercholesterolemia (FH) or severe hypercholesterolemia participants who had
tolerated the treatment regimen in Protocol 301012-CS5 (NCT00607373), 301012-CS7
(NCT00706849) or MIPO3500108 (NCT00794664) and satisfactorily completed the study through to
Week 28 were eligible for participation in this open label treatment extension study for up
to 4 years or until mipomersen was commercially available, whichever comes first. Consenting
participants who had 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 was commercially available, whichever comes first. All
participants, who entered the study, received 200 mg mipomersen (ISIS 301012) subcutaneously
(s.c.) every week, including those who were randomized to placebo in their initial study.
Participants who were originally enrolled in Protocol 301012-CS5 (NCT00607373) and weighed
<50 kg received 160 mg every week. Dose adjustments (70 mg injections administered three
times per week, on separate days) were allowed for participants who were not tolerating or
who 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, 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 was to be
performed every 4-10 weeks during the treatment period. Plasma trough mipomersen (ISIS
301012) levels was to be measured to estimate exposure. Participants who completed dosing or
who discontinued prematurely from the study for any reason was 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. Participants were required to return to the study center for clinical evaluation
and clinical laboratory tests every 8 weeks during the safety follow-up period.

Inclusion Criteria:

- Satisfactory completion of dosing in their initial study (Protocol 301012-CS5
[NCT00607373], 301012-CS7 [NCT00706849], 301012-CS17 [NCT00477594], or MIPO3500108
[NCT00794664])

Exclusion Criteria:

- Had any new condition or worsening of existing condition which in the opinion of the
Investigator would make the participant unsuitable for enrollment, or could interfere
with the participant participating in or completing the study