Treatment with AMG 145 reduces LDL cholesterol

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. 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.

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.