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Evolocumab Reduces LDL Cholesterol in Statin-Treated Patients
Results from the phase III LAPLACE-2 trial, which evaluated 1,896 patients with high cholesterol, have shown that treatment with subcutaneous (SC) evolocumab (Amgen), administered at a dosage of 140 mg every 2 weeks or 420 mg monthly, in combination with different daily doses of statin therapy significantly reduced mean low-density lipoprotein cholesterol (LDL-C) levels regardless of statin dose. The new findings were published in JAMA.
Evolocumab, an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) — a protein that reduces the liver's ability to remove LDL-C from the blood — reduced mean LDL-C levels by 55% to 76% from baseline compared with placebo and by 38% to 47% from baseline compared with ezetimibe (Zetia, Merck) (P < 0.001). The most common adverse events (AEs) in the evolocumab combined group were back pain, arthralgia, headache, muscle spasms, and pain in an extremity.
According to the Centers for Disease Control and Prevention (CDC), more than 71 million adults in the U.S. have high LDL-C, or “bad” cholesterol. Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.
The LAPLACE-2 (LDL-C Assessment With PCSK9 MonoclonaL Antibody Inhibition Combined With Statin ThErapy-2) trial was a 12-week, phase III, randomized, double-blind, placebo- and ezetimibe-controlled study designed to evaluate the safety, tolerability, and efficacy of evolocumab in 1,896 patients with primary hypercholesterolemia and mixed dyslipidemia (LDL-C ≥ 80 mg/dL) when added to statin therapy.
The patients were randomly assigned to one of 24 treatment groups in a two-step randomization process. Eligible patients were initially assigned to one of five open-label background statin treatments: atorvastatin 10 mg, atorvastatin 80 mg, rosuvastatin 5 mg, rosuvastatin 40 mg, or simvastatin 40 mg daily. Patients given atorvastatin were then assigned to one of six treatment groups: evolocumab every 2 weeks and oral placebo; evolocumab every month and oral placebo; SC placebo every 2 weeks and oral placebo, SC placebo every month and oral placebo; SC placebo every 2 weeks and ezetimibe 10 mg; or SC placebo every month and ezetimibe 10 mg. Patients given rosuvastatin or simvastatin were then randomly assigned to one of four treatment groups: evolocumab every 2 weeks; evolocumab every month; SC placebo every 2 weeks; or SC placebo every month.
The study’s co-primary endpoints were the mean percent change from baseline in LDL-C at weeks 10 and 12 and the percent change in LDL-C reduction at week 12.
Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation, thereby reducing the liver’s ability to remove LDL-C from the blood. Evolocumab is designed to bind to PCSK9 and to inhibit PCSK9 from binding to LDL receptors on the liver’s surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
Evolocumab is being evaluated in 20 studies, with a combined planned enrollment of nearly 30,000 patients, in the PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations) clinical trial program.
Source: Amgen; May 13, 2014.