Adding evolocumab in combination with statins can help reduce high cholesterol

February 3, 2014

Adding evolocumab (Amgen) to statin therapy may help patients control their low-density lipoprotein cholesterol (LDL-C) levels when high doses of statins are not sufficient, according to results from a recent phase 3 study.

Adding evolocumab (Amgen) to statin therapy may help patients control their low-density lipoprotein cholesterol (LDL-C) levels when high doses of statins are not sufficient, according to results from a recent phase 3 study.

Evolocumab is 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

The phase 3 LAPLACE-2 (LDL-C Assessment with PCSK9 MonoclonaL Antibody Inhibition Combined with Statin ThErapy-2) randomized, multicenter, double-blind, placebo- and ezetimibe-controlled trial evaluated evolocumab in 1,896 patients with primary hypercholesterolemia and mixed dyslipidemia (LDL-C >80 mg/dL) when added to statin therapy.

Patients were randomly assigned to 1 of 24 treatment groups in a 2-step randomization. Eligible patients were initially randomly assigned to 1 of 5 open-label background statin treatments: Atorvastatin 10 mg, atorvastatin 80 mg, rosuvastatin 5 mg, rosuvastatin 40 mg, or simvastatin 40 mg daily. Patients randomly assigned to atorvastatin were then randomly assigned to 1 of 6 treatment groups: Evolocumab every 2 weeks and oral placebo, evolocumab every month and oral placebo, subcutaneous placebo every 2 weeks and oral placebo, subcutaneous placebo every month and oral placebo, subcutaneous placebo every 2 weeks, and ezetimibe 10 mg, or subcutaneous placebo every month and ezetimibe 10 mg. Patients randomly assigned to rosuvastatin or simvastatin were then randomized to 1 of 4 treatment groups: Evolocumab every 2 weeks, evolocumab every month, subcutaneous placebo every 2 weeks, or subcutaneous placebo every month.

The coprimary end points in the study were met, including 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. Cosecondary efficacy end points included means at weeks 10 and 12 and at week 12 for the following: LDL-C <70 mg/dL; absolute change from baseline in LDL-C; and the percentage change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C, and very low-density lipoprotein cholesterol (VLDL-C).

Safety was balanced across treatment groups. No adverse events (AEs) occurred in ≥ 2 percent of the evolocumab-combined group. The most common AEs in the evolocumab-combined group were back pain, arthralgia, headache, muscle spasms, and pain in extremity.


According to the Centers for Disease Control and Prevention, more than 71 million American adults have high LDL-C. Elevated LDL-C is recognized as a major risk factor for cardiovascular disease. A multinational survey of almost 10,000 patients with high cholesterol on statin therapy found approximately one-third of patients did not attain their LDL-C goal.

“The objective of the LAPLACE-2 trial was to understand the overall safety, tolerability and efficacy of evolocumab in combination with statin therapy compared to placebo and ezetimibe in 1,896 patients with high cholesterol. “Based on our phase 2 experience, we chose coprimary end points to characterize the efficacy of PCSK9 inhibition with a fully human monoclonal antibody,” according to Scott Wasserman, MD, FACC, executive medical director of clinical development at Amgen.


“As statins continue to be an important treatment option in patients with high cholesterol, we are very encouraged by the phase 3 data from the LAPLACE-2 study,” said Sean E. Harper, MD, executive vice president of research and development at Amgen.

Details of the phase 3 LAPLACE-2 study results will be presented in March at the American College of Cardiology (ACC) 63rd Annual Scientific Session and submitted for publication.