Circulation Publishes Results From RUTHERFORD Study Which Showed AMG 145 Significantly Reduced LDL Cholesterol In Patients With Heterozygous Familial Hypercholesterolemia

AMG 145 Combination Therapy With Statins Reduced LDL Cholesterol up to 56 Percent
Genetic Condition Creates Risk of Aggressive and Premature Cardiovascular Disease
Data Presented Simultaneously at American Heart Association Scientific Sessions 2012

THOUSAND OAKS, Calif., Nov. 5, 2012 /PRNewswire/ -- Amgen (NASDAQ:AMGN) 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. 

RUTHERFORD Study Design
RUTHERFORD (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study) was a randomized, double-blind, placebo-controlled study that evaluated AMG 145, dosed subcutaneously Q4W, in 168 patients with an LDL-C >100 mg/dL who were on a stable dose of statin, with or without ezetimibe. Patients were randomized to three treatment groups: AMG 145 at 350 mg, AMG 145 at 420 mg or placebo administered subcutaneously every four weeks. 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.

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