Amgen announced that treatment with AMG 145 in combination with statin therapy, with or without ezetimibe (Zetia; Merck), resulted in a reduction in low density lipoprotein cholesterol (LDL-C), by up to 56% in patients with heterozygous familial hypercholesterolemia (HeFH) in the Phase 2 RUTHERFORD study. AMG 145 is an investigational fully human monoclonal antibody directed against PCSK9, a protein that reduces the liver’s ability to remove LDL-C from the blood.
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 350mg, AMG 145 at 420mg or placebo administered subcutaneously every four weeks.
Treatment with AMG 145 every four weeks resulted in a significant LDL-C decrease vs. 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% and 55% with AMG 145 350mg and 420mg, respectively, compared to a 1% increase with placebo (P<0.001 for both dose groups). At Week 12, treatment with AMG 145 350mg and 420mg every four weeks resulted in 70% and 89% of patients reaching LDL-C levels of <100mg/dL and 44% and 65% achieving <70mg/dL, respectively, compared to 2% and 0% of placebo subjects, respectively. Favorable reductions in total cholesterol, non-HDL-C, Lp(a) and ApoB were consistent with the reductions in LDL-C.
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