LOS ANGELES — Patients at CV risk who are unable to tolerate effective doses of statins experienced reductions in LDL levels of up to 51% with AMG 145, an investigational, anti-PCSK9 antibody, Evan A. Stein, MD, reported here.
The GAUSS study was initiated to test the safety, tolerability and efficacy of subcutaneous AMG145 (Amgen, Inc.), which binds to PCSK9 in the circulation and blocks its interaction with the LDL receptor and thus increases cholesterol removal from the blood stream. Its use was compared with ezetimibe (Zetia, Merck) in statin-intolerant patients at high and moderate CV risk.
The 12-week, randomized, double blind, controlled, dose-ranging study was conducted between July 2011 and May 2012 and enrolled 236 patients. Patients were randomly assigned to one of five groups: AMG145 280 mg, 350 mg or 420 mg alone; AMG 145 420 mg plus 10 mg ezetimibe; or 10 mg ezetimibe plus placebo. AMG 145 and placebo were administered subcutaneously every 4 weeks.
At 12 weeks, mean LDL, measured by ultracentrifugation, decreased 41% for patients assigned AMG 145 280 mg; 43% for AMG 145 350 mg; 51% for AMG 145 420 mg; 63% for AMG 145 420 mg plus ezetimibe; and 15% for placebo plus ezetimibe (P<.001 vs. placebo and ezetimibe).
Evan A. Stein
Sixty-one percent of patients assigned AMG 145 420 mg achieved an LDL goal of <100 mg/dL and up to 29% reached <70 mg/dL. When combined with ezetimibe, 90% of patients reached the goal of <100 mg/dL and 62% reached <70 mg/dL, according to Stein, from the Metabolic and Atherosclerosis Research Center in Cincinnati, Ohio.
Data also demonstrated benefits in total cholesterol, non-HDL, lipoprotein(a), apolipoprotein B, and the ratios of total cholesterol/HDL and ApoB/ApoA1. AMG 145 alone or with ezetimibe increased HDL modestly, from 6% to 12%, compared with a 1% decrease with ezetimibe alone (P<.001). Small, nonsignificant reductions in triglycerides and VLDL were observed with AMG 145 compared with ezetimibe alone. Free PCSK9 levels declined by 48% from baseline to 12 weeks with AMG 145 and by 2% with ezetimibe alone, according to a press release.
Myalgia was the most common treatment-emergent adverse event during the study. Other adverse events included nasopharyngitis, nausea and fatigue. Overall, the drug was well tolerated and efficacious, with or without ezetimibe, Stein said. However, larger studies are needed to confirm these findings, he added.
The mean age of patients in the GAUSS study was 62 years. Sixty-four percent were women. Mean baseline LDL level was 193 mg/dL. – by Samantha Costa
For more information:
Stein E. Late breaking clinical trials: Novel treatments for managing lipid disorders. Presented at: the American Heart Association Scientific Sessions; Nov. 3-7, 2012; Los Angeles.
Sullivan D. JAMA. 2012;doi:10.1001/jama.2012.25790.
Disclosure: Stein reports being a paid consultant for Amgen and Regeneron-Sanofi.