Evolocumab meets primary end point of LDL cholesterol reduction in phase 3 study

January 9, 2014

Evolocumab (Amgen) may offer a new treatment option for patients with dyslipidemia, according to new data from a phase 3 study.

Evolocumab (Amgen) may offer a new treatment option for patients with dyslipidemia, according to new data from a 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 low-density lipoprotein cholesterol (LDL-C) from the blood.

The DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) study, designed to evaluate the long-term (52-week) safety, tolerability and efficacy of evolocumab in patients with hyperlipidemia at risk for cardiovascular disease, met its primary end point of percent reduction from baseline in LDL-C at week 52.

Background lipid-lowering therapy was optimized to 1 of 4 treatment groups (diet alone; diet plus atorvastatin 10 mg; diet plus atorvastatin 80 mg; and diet plus atorvastatin 80 mg plus ezetimibe 10 mg) for individual patients based on their LDL-C and cardiovascular risk according to the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III risk categories. After optimization, patients were maintained on therapy for at least 4 weeks. A total of 901 patients with a fasting LDL-C ≥ 75 mg/dL were then randomly assigned and received monthly subcutaneous evolocumab 420 mg or placebo in combination with background lipid-lowering therapy.

Evolocumab significantly reduced LDL-C, as measured by the accepted standard, preparative ultracentrifugation, from baseline at week 52 compared to placebo. LDL-C reduction at week 12 was consistent with the long-term efficacy at week 52, according to the study results. The mean percent reduction in LDL-C, or "bad" cholesterol, was consistent with the results observed in the 52-week analysis of the phase 2 OSLER (Open Label Study of Long TERm Evaluation Against LDL-C) study.

Safety was balanced across treatment groups. The most common adverse events (> 5% in evolocumab) were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.

“As a fully human monoclonal antibody directed against PCSK9, evolocumab, is an investigational therapy in a growing and emerging class of new LDL-C lowering therapies that may provide patients with high LDL-C despite optimal lipid-lowering therapy an important therapeutic option to treat their elevated LDL-C and cardiovascular risk,” according to Scott M. Wasserman, MD, FACC, executive medical director of clinical development at Amgen.

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.