Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects With Genetic LDL Disorders

This phase 2/3 open-label extension study was designed to characterize the safety and
tolerability of long-term administration of evolocumab to adults and adolescents with severe
FH (HoFH or non-HoFH severe FH). Participants not on lipid apheresis at enrollment or within
the prior 8 weeks initiated treatment with evolocumab 420 mg once monthly (QM). Participants
on lipid apheresis at enrollment initiated treatment with evolocumab 420 mg once every 2
weeks (Q2W). Dose frequency changes (420 mg QM vs 420 mg Q2W) were permitted at week 12, 24,
or other visits with Sponsor approval. Participants with < 5% LDL-C reduction from baseline
and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) < 100 ng/mL could
discontinue evolocumab. If serum unbound PCSK9 was ≥ 100 ng/mL with QM dosing, the
participant could switch to evolocumab 420 mg Q2W treatment. Participants on apheresis with ≥
5% LDL-C reduction from baseline and serum unbound PCSK9 < 100 ng/mL with Q2W treatment could
switch to QM dosing.

Participants were to continue to receive open-label evolocumab for up to 5 years or until
evolocumab became commercially available in the relevant patient population, whichever
occurred first.

Inclusion Criteria:

- Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent
protocol and have a diagnosis of familial hypercholesterolemia.

OR

- Have a diagnosis of familial hypercholesterolemia AND

- Males and females ≥ 12 to ≤ 80 years of age

- Stable low-fat diet and lipid-lowering therapies for at least 4 weeks

- Low-density lipoprotein cholesterol (LDL-C) >= 130 mg/dl (3.4 mmol/L) for subjects
without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C >= 100
mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis
patients have no LDL-C entry requirement

- Fasting triglycerides ≤ 400 mg/dL(4.5 mmol/L)

- Body weight of > 40 kg or greater at screening for subjects less than 18 years of age

Exclusion Criteria:

- New York Heart Failure Association (NYHA) class III or IV or last known left
ventricular ejection fraction < 30%

- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI),
coronary artery bypass graft (CABG) or stroke within 3 months of screening

- Planned cardiac surgery or revascularization

- Uncontrolled cardiac arrhythmia

- Uncontrolled hypertension