Trial of a PCSK9 inhibitor in heterozygous familial hypercholesterolemia

1. Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial
Hypercholesterolemia Disorder (RUTHERFORD): Interim Results from a
Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial
• Background: Heterozygous familial • Results: At week 12, percent change in LDL-C levels
hypercholesterolemia (HeFH) is a common genetic were -43% in the 350 mg AMG145 group, -55% in the
disorder that causes many patients not to reach LDL-C 420 mg AMG145 group and an increase of 1% in the
treatment goals, even with statin therapy. Plasma placebo group. No serious treatment-related adverse
proprotein convertase subtilisin/kexin type 9 (PCSK9) events occurred.
binds LDL receptors, therefore increasing levels of LDL-
• Conclusion: AMG145 may provide effective additional
C in the blood. Phase 1 studies of a human monoclonal
LDL-C lowering treatment in HeFH patients on intensive
antibody to PCSK9, AMG145, have shown tolerance
statin therapy.
and effectiveness in lowering LDL-C.
• Purpose: To assess the effectiveness and safety of Percent of Patients Treated to LDL-C Goal at Week 12
AMG145 in patients with HeFH.
Treatment LDL-C < 100 LDL-C < 70
• Methods: In this 12-week, randomized, double-blind, mg/dL mg/dL
placebo-controlled study, 167 patients were
350 mg AMG145 70% 44%
randomized to one of 3 treatments: 350 mg of
AMG145, 420 mg of AMG145 or placebo administered
420 mg AMG145 89% 65%
subcutaneously every 4 weeks. Primary endpoint was
percent change in LDL-C levels from baseline to 12
Placebo 2% 0%
weeks.
Presented by: Raal F, AHA Scientific Sessions, Los Angeles © 2012, American Heart Association. All rights reserved.