THOUSAND OAKS, Calif., Nov. 5, 2012 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced positive results from the AMG 145 Phase 2 GAUSS study, in patients with high cholesterol who cannot tolerate statins. Reductions of up to 51 percent were observed in low density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, with AMG 145 and 63 percent with the combination of AMG 145 and ezetimibe, compared to 15 percent with ezetimibe alone. 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 Journal of the American Medical Association and simultaneously presented in an oral session at the American Heart Association Scientific Sessions 2012.
At week 12, the mean decrease from baseline in LDL-C, measured by preparative ultracentrifugation, was 41 percent in the AMG 145 280 mg group; 43 percent in the AMG 145 350 mg group; 51 percent in the AMG 145 420 mg group; 63 percent in the AMG 145 420 mg/ezetimibe 10 mg group; and 15 percent in the placebo/ezetimibe 10 mg group. The reduction in LDL-C with all doses of AMG 145 was significantly greater than that observed with ezetimibe alone ( p<0.001).
LDL-C is recognized as a major contributor of risk for cardiovascular disease.[i] Despite the availability of various treatments for lowering LDL-C, it is estimated that in two-thirds of treated high-risk patients, LDL-C is not well controlled.[ii], [iii] While statins are effective, it is estimated that 5 to 15 percent of patients cannot tolerate statins, primarily due to muscle-related side effects.[iv]
"Close to a million people in the USA alone who are treated with statins cannot tolerate them, or the doses needed for effective cholesterol control. These patients who are at risk for heart disease or recurrent heart attacks have few effective alternatives," said Evan Stein, M.D., Ph.D., director of the Metabolic and Atherosclerosis Research Center in Cincinnati. "In the GAUSS study, AMG 145 significantly reduced LDL or 'bad' cholesterol in these patients with previous muscle problems on statins."Other Efficacy ResultsAMG 145 also showed reductions in total cholesterol, non-HDL-C, ApoB, and the ratios of total cholesterol/HDL-C and ApoB/ApoA1. In this trial, lipoprotein (a), or Lp(a), was reduced by 20 to 26 percent with AMG 145 and 29 percent with the combination of AMG 145 and ezetimibe (all p<0.01 to p<0.001 versus the ezetimibe alone group). AMG 145 alone or with ezetimibe increased HDL-C modestly, from 6 percent to 12 percent, compared with a 1 percent decrease with ezetimibe alone ( p<0.001). Increases were also seen in ApoA1, with all groups treated with AMG 145 showing greater responses than those treated with ezetimibe alone ( p<0.05 or p<0.01). Small, non-significant reductions in triglycerides and very low-density lipoprotein cholesterol (VLDL-C) were seen with AMG 145 compared with ezetimibe alone. Free PCSK9 levels at week 12 declined by up to 48 percent from baseline with AMG 145 and by 2 percent with ezetimibe alone. The most common adverse events (AEs) for AMG 145 in this trial were myalgia, nasopharyngitis, nausea and fatigue.