Press Release Details

THOUSAND OAKS, Calif., Nov. 6, 2012 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that results from the LAPLACE-TIMI 57 and MENDEL Phase 2 studies evaluating AMG 145 in hypercholesterolemic patients with or without statins, respectively, showed that treatment with AMG 145 resulted in a statistically significant reduction in low-density lipoprotein (LDL) cholesterol. The two studies were presented today at the American Heart Association Scientific Sessions 2012 and simultaneously published in The Lancet.

AMG 145 is an investigational fully human monoclonal antibody directed against PCSK9, a protein that reduces the liver's ability to remove LDL-C, or "bad" cholesterol from the blood.  LDL-C is 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]

LAPLACE-TIMI 57 Primary Results

• Results from the LAPLACE-TIMI 57 study showed that all six dose regimens of AMG 145 significantly decreased LDL-C, measured by preparative ultracentrifugation, from baseline compared to placebo at week 12 in patients at risk for cardiovascular disease already on statin therapy (p<0.0001).
• In these at risk patients, LAPLACE-TIMI 57 showed the addition of AMG 145 to statin therapy, with or without ezetimibe, achieved significant decreases in LDL-C.
• At week 12, AMG 145 reduced LDL-C, measured by preparative ultracentrifugation, by up to 66 percent when dosed every two weeks (Q2W) and up to 50 percent when dosed very four weeks (Q4W), compared to placebo (p<0.001 for the highest dose vs. placebo). 
  • The mean reduction in LDL-C versus placebo for AMG 145 dosed Q2W was 42 percent in the 70 mg group; 60 percent in the 105 mg group; and 66 percent in the 140 mg group.
  • The mean reduction in LDL-C versus placebo for AMG 145 dosed Q4W was 42 percent in the 280 mg group; 50 percent in the 350 mg group; and 50 percent in the 420 mg group. 
• The most commonly reported adverse events (AEs) for AMG 145 were nasopharyngitis, cough and nausea.

"Statins have been a critical tool in the management of high cholesterol, but even at high doses, statins do not always achieve the targeted level of LDL (bad) cholesterol in our high risk patients," said Robert Giugliano, M.D., Brigham and Women's Hospital, Cardiovascular Medicine. "The LAPLACE-TIMI 57 study is very relevant in that the addition of AMG 145 to background therapy with statins resulted in significant reductions in LDL-cholesterol at all the doses tested."

Efficacy and Safety of a Fully Human Monoclonal Antibody Against PCSK9 as Monotherapy for Hypercholesterolemia: Results from the MENDEL Study, a Global Phase 2 Trial of AMG 145 

• MENDEL is the first monotherapy study of a PCSK9-inhibitor, and evaluated AMG 145 in patients who were not taking a statin.
• Results of the study at week 12 demonstrated that AMG 145, dosed Q2W or Q4W, significantly reduced LDL-C, measured by preparative ultracentrifugation, compared to placebo (p<0.001).
• At week 12, treatment with AMG 145 reduced LDL-C, measured by preparative ultracentrifugation, by up to 47 percent in the groups dosed Q2W; and up to 53 percent from baseline in the groups dosed Q4W, compared to placebo (p<0.001 for the highest dose vs. placebo).
  • The mean decrease in LDL-C from baseline for AMG 145 dosed Q2W was 41 percent in the 70 mg group; 44 percent in the 105 mg group; and 51 percent in the 140 mg group compared to four percent for placebo.
  • The mean decrease in LDL-C from baseline for AMG 145 dosed Q4W was 39 percent in the 280 mg group; 43 percent in the 350 mg group; and 48 percent in the 420 mg group compared to five percent increase for placebo.
• The most commonly reported AEs for AMG 145, were upper respiratory tract infection, nasopharyngitis and diarrhea.

"In the MENDEL study, AMG 145 monotherapy showed robust reductions in serum LDL-C with both the Q2W and Q4W dosing regimens in patients with high cholesterol regardless of sex, age, race or cardiovascular risk factors," said Michael Koren, M.D., C.P.I. of Jacksonville Center for Clinical Research. "This study provides support that treatment with AMG 145 may be an alternative approach for LDL-C reduction in patients who cannot take statins."

These studies are two of four Phase 2 studies of AMG 145 being presented at the American Heart Association Scientific Sessions 2012.

LAPLACE-TIMI 57 Study Design
LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 monoclonaL Antibody inhibition Combined with statin thErapy – Thrombolysis In Myocardial Infarction-57) is a Phase 2 randomized, double-blind, dose-ranging, placebo-controlled study that included eight treatment arms to evaluate the efficacy, safety and tolerability of AMG 145, administered subcutaneously, in 629 patients at risk for cardiovascular disease with LDL-C > 85 mg/dL when added to a stable dose of statin with or without ezetimibe.  Treatment arms included AMG 145 (70 mg, 105 mg and 140 mg) versus placebo Q2W and AMG 145 (280 mg, 350 mg and 420 mg) versus placebo Q4W.  The primary endpoint of the study was the percent change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12. Secondary efficacy endpoints included the absolute change from baseline in LDL-C at week 12 and the percentage changes from baseline to week 12 in non-high-density lipoprotein (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio and ApoB/ApoA1 ratio.

MENDEL Study Design
MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy For Easing Lipid Levels) is a Phase 2 randomized, multi-center, double-blind, controlled trial designed to evaluate the efficacy, safety and tolerability of AMG 145 in 406 patients with low cardiovascular risk (LDL-C > 100 mg/dL and < 190 mg/dL) who were not receiving statin therapy. AMG 145 was evaluated across nine treatment groups, including AMG 145 at 70 mg, 105 mg and 140 mg dosed Q2W compared to placebo Q2W; and AMG 145 at 280 mg, 350 mg and 420 mg dosed Q4W compared to placebo Q4W; or daily ezetimibe 10 mg. The primary endpoint was percentage change from baseline in LDL-C, measured by preparative ultracentrifugation, at week 12. Secondary efficacy endpoints included the absolute change from baseline in LDL-C at week 12 and the percentage changes from baseline at week 12 in non-high-density lipoprotein (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio and ApoB/ApoA1 ratio.

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 AHA. 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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[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 2011 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.

SOURCE Amgen