LAPLACE-TIMI 57: AMG 145 Reduces LDL-C Levels
AMG 145, a human monoclonal antibody to PCSK9, significantly reduced LDL cholesterol (LDL-C) levels in patients with hypercholesterolemia on a stable regimen of statin with or without ezetimibe, according to an analysis from the LAPLACE-TIMI 57 trial released on Nov. 6 as part of AHA 2012 and published simultaneously in The Lancet.
LAPLACE-TIMI 57 was a phase 2, dose-ranging study that looked at 631 patients between the ages of 18 and 80 years who were on a stable dose of statin with or without ezetimibe, and with LCL-C greater than 2•2 mmol/L. Patients were randomly assigned to AMG 145 70 mg (n=79), 105 mg (n=79), or 140 mg (n=78), or matching placebo (n=78) every two weeks; or subcutaneous injections of AMG 145 280 mg (n=79), 350 mg (n=79), and 420 mg (n=80), and matching placebo (n=79) every four weeks. At the end of the dosing intervals at week 12, the mean LDL-C concentrations were reduced generally dose dependently by AMG 145 every two weeks (ranging from 41•8 percent to 66•1 percent; p<0•0001 for each dose vs. placebo) and AMG 145 every four weeks (ranging from 41•8 percent to 50•3 percent; p<0•0001).
Clinical practice guidelines for the management of hypercholesterolemia have established an LDL-C goal of <100 mg/dL, with an optional goal of <70 mg/dL for high-risk patients. According to the study authors, these new results suggest AMG 145 may be a viable option for meeting guideline-recommended goals for the high-risk group.
In addition, two other trials focused on AMG 145 were also released Nov. 6 at AHA 2012. The AMG 145 trial found that in high-risk patients within the LAPLACE-TIMI 57 trial, treatment with AMG 145 vs. placebo "reduced LDL-C by up to 64 percent at week 12," while the MENDEL trial, which was simultaneously published in The Lancet, found that AMG 145 "significantly reduced LDL-C concentrations in all dose groups."
These trials falls on the heels of two additional trials released Nov. 5 at AHA 2012 focused on AMG145. Results from the GAUSS trial showed that subcutaneous administration of AMG145 significantly reduced LDL cholesterol levels and was associated with short-term tolerability in statin-intolerant patients, while the RUTHERFORD trial showed that AMG145 administered every four weeks yielded "rapid and substantial reductions in LDL-C in heterozygous familial hypercholesterolemia patients despite intensive statin use, with or without ezetimibe, with minimal adverse events and good tolerability."
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