AMG 145 significantly reduced LDL cholesterol in patients

Amgen today announced that treatment with AMG 145 in combination with statin therapy, with or without ezetimibe, resulted in a reduction in low density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, by up to 56 percent 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. The study was published today in Circulation and simultaneously presented in a late-breaking clinical trial session at the American Heart Association Scientific Sessions 2012.

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 Frederick Raal, M.D., Ph.D., Carbohydrate & Lipid Metabolism Research Unit, Division of Endocrinology & Metabolism, Department of Medicine, University of the Witwatersrand, Johannesburg. “Data from the RUTHERFORD study suggests that using AMG 145 as an add-on therapy to statins helped these high-risk patients achieve LDL-C goals and offers promise for the treatment of HeFH.”

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.