HeFH is one of the most common genetic disorders, affecting at least one out of every 500 people worldwide. HeFH causes severe elevations in total cholesterol and LDL-C, leading to the premature development of cardiovascular disease and early cardiovascular morbidity and mortality.
In the RUTHERFORD trial, treatment with AMG 145 every four weeks (Q4W) resulted in a significant LDL-C decrease versus placebo in HeFH patients on lipid-lowering therapy (statins with or without ezetimibe). At week 12, LDL-C reduction, measured by preparative ultracentrifugation, was 43 percent and 55 percent with AMG 145 350 mg and 420 mg, respectively, compared to a 1 percent increase with placebo (p<0.001 for both dose groups). At week 12, treatment with AMG 145 350 mg and 420 mg Q4W resulted in 70 percent and 89 percent of patients reaching LDL-C levels of <100 mg/dL and 44 percent and 65 percent achieving <70 mg/dL, respectively, compared to 2 percent and 0 percent of placebo subjects, respectively. Favorable reductions in total cholesterol, non-HDL-C, Lp(a) and ApoB were consistent with the reductions in LDL-C.
"Despite existing therapies and maintaining a healthy lifestyle, patients with heterozygous familial hypercholesterolemia are prematurely at risk for serious cardiovascular disease due to the difficulty in reducing their LDL-C levels," said
The most common adverse events (AEs) for AMG 145 in this trial were nasopharyngitis, injection-site reaction and headache.
This study is one of four Phase 2 studies of AMG 145 being presented at the American Heart Association Scientific Sessions 2012.
RUTHERFORD Study Design
RUTHERFORD (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study) was a randomized, double-blind, placebo-controlled study that evaluated AMG 145, dosed subcutaneously Q4W, in 168 patients with an LDL-C >100 mg/dL who were on a stable dose of statin, with or without ezetimibe. Patients were randomized to three treatment groups: AMG 145 at 350 mg, AMG 145 at 420 mg or placebo administered subcutaneously every four weeks. The primary endpoint was percentage change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12.
About AMG 145
AMG 145 is a fully human monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that reduces the liver's ability to remove LDL-C from the blood and thereby causes bad cholesterol to increase. AMG 145, developed by
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