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More phase III results showed that Amgen's investigational PCSK9 inhibitor evolocumab -- also called AMG 145 -- significantly reduced LDL cholesterol within 12 weeks, this time in patients who were also taking a statin.
Top-line results of the LAPLACE-2 trial revealed that the trial met both of its coprimary endpoints -- the percent reduction from baseline in LDL cholesterol at week 12 and the mean percent reduction from baseline in LDL cholesterol at weeks 10 and 12.
In its announcement, Amgen said the reductions were consistent with those seen in the phase II LAPLACE-TIMI 57 and MENDEL studies, which demonstrated drops of 39% to 66% through 12 weeks.
Evolocumab is a human monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9), which prevents the protein from marking LDL receptors on the liver for destruction. The greater numbers of LDL receptors allow for more LDL cholesterol to be cleared from the body.
LAPLACE-2 compared evolocumab with placebo and ezetimibe in 1,896 patients who were also on a variety of background statin regimens. Evolocumab was administered subcutaneously at a dose of 140 mg every 2 weeks or 420 mg monthly.
There were 24 treatment groups stemming from the different dosing strategies of evolocumab, the two comparators, and the use of multiple doses of atorvastatin and rosuvastatin (Crestor) and a single dose of simvastatin to form the background statin regimens.
Amgen reported that evolocumab was well-tolerated in the trial, with no adverse events occurring in 2% or more of patients in the combined evolocumab groups. The most common adverse events were back pain, arthralgia, headache, muscle spasms, and extremity pain.
LAPLACE-2 is part of a 13-trial phase III program for the drug that plans to enroll more than 28,000 patients. The company announced top-line results of two other phase III trials -- MENDEL-2 and DESCARTES -- last month. Those trials also met their primary endpoints, with LDL cholesterol reductions reportedly in the range of those seen in phase II.
From the American Heart Association: