Journal of the American Medical Association Publishes AMG 145 Phase 2 GAUSS Study Showing Significant Reductions In LDL Cholesterol In Statin-Intolerant Patients

AMG 145 Reduced LDL Cholesterol by up to 51 Percent in a Difficult-to-Treat Population

Data Simultaneously Presented at American Heart Association Scientific Sessions 2012

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Nov 05, 2012, 02:33 ET

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 Results
AMG 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.

This study is one of four Phase 2 studies of AMG 145 being presented at the American Heart Association Scientific Sessions 2012.

GAUSS Study Design
The GAUSS study (Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin intolerant Subjects) was a 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study to assess the efficacy, safety and tolerability of AMG 145 in 160 patients ages 18 to 75 years who could not tolerate effective statin doses due to muscle-related side effects. Patients were randomized to five groups: AMG 145 given subcutaneously (SC) at three doses: 280 mg, 350 mg and 420 mg; AMG 145 420 mg SC plus daily ezetimibe 10 mg; or placebo SC and daily ezetimibe 10 mg. Dosing was every four weeks in all groups. The primary endpoint was percentage change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12.

Webcast Information
Amgen will hold an analyst/investor event on Tuesday, Nov. 6, at 7:00 p.m. Pacific Standard Time to discuss data presented at the American Heart Association Scientific Sessions 2012. A webcast of the event can be found on Amgen's website at www.amgen.com, under Investors. The audio webcast will be archived and available for replay for at least 72 hours.

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 Amgen scientists, binds to PCSK9 circulating in the blood and prevents PCSK9 from binding to LDL receptors in the liver. Without PCSK9 bound to them, the LDL receptors can take up and remove LDL-C from the blood, recycle and remain available for binding additional LDL-C. The Amgen Phase 2 program for AMG 145 enrolled more than 2,000 patients across seven studies to evaluate the effects of AMG 145 across multiple patient populations who may benefit from additional cholesterol lowering treatment options. The Phase 2 program is evaluating the treatment of hyperlipidemia with AMG 145 in combination with statins, in patients with hyperlipidemia who cannot tolerate statins, as a stand-alone treatment in patients with hyperlipidemia, and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous and homozygous familial hypercholesterolemia.

About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward-Looking Statements
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[i] American Heart Association. (2012). Why Cholesterol Matters. Retrieved September 17, 2012, from http://www.heart.org/HEARTORG/Conditions/Cholesterol/WhyCholesterolMatters/Why-Cholesterol-Matters_UCM_001212_Article.jsp.
[ii] AHA 201 Update Online. http://circ.ahajournals.org/content/123/4/e18.full. Page 119. Accessed November 2012.
[iii] Dyslipidaemia. The Lancet, 362 (9385): 717–31.doi:10.1016/S0140-6736(03)14234-1.
[iv] Fernandez G, Spatz ES, Jablecki C, Phillips PS. "Statin myopathy: a common dilemma not reflected in clinical trials." Cleve Clin J Med. 2011;78:393-403.

SOURCE Amgen