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Journal of the American Medical Association Publishes AMG 145 Phase 2 GAUSS Study Showing Significant Reductions In LDL Cholesterol In Statin-Intolerant Patients
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
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.
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
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[ii] AHA 201 Update Online. http://circ.ahajournals.org/content/123/4/e18.full. Page 119. Accessed
[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.