Amgen, an American multinational biopharmaceutical company, reported the phase III results from DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) study evaluating the long-term 52-week safety and efficacy of evolocumab for the treatment of high cholesterol has met its primary endpoint of percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 52. The mean percent reduction in LDL-C, or "bad" cholesterol, was consistent with the results observed in the 52-week analysis of the phase II OSLER (Open Label Study of Long TERm Evaluation Against LDL-C) 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 DESCARTES study evaluated safety, tolerability and efficacy in 901 patients with high LDL-C and a range of cardiovascular risk. Background lipid-lowering therapy was optimized to one of four 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. Patients with a fasting LDL-C = 75 mg/dL were then randomized to receive 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.
Safety was balanced across treatment groups. The most common adverse events (> 5 per cent in evolocumab) were nasopharyngitis, upper respiratory tract infection, influenza and back pain.
"Data from the phase III DESCARTES study of evolocumab add to the promising safety and efficacy data we recently saw in the MENDEL-2 study and 52-week phase II OSLER study," said Sean E Harper, MD, executive vice president of Research and Development at Amgen. "These data contribute to the growing body of research suggesting that evolocumab may offer a new treatment option for patients with dyslipidemia."
DESCARTES is a phase III randomized, multicenter, double-blind, placebo-controlled study designed to evaluate the long-term (52-week) safety, tolerability and efficacy of evolocumab in patients with hyperlipidemia at risk for cardiovascular disease. Background lipid-lowering therapy was optimized to one of four 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 four weeks. A total of 901 patients with a fasting LDL-C = 75 mg/dL were then randomized and received monthly subcutaneous evolocumab 420 mg or placebo in combination with background lipid-lowering therapy.
The primary endpoint was percent change from baseline in LDL-C, measured by the accepted standard, preparative ultracentrifugation, after 52 weeks of treatment. Secondary efficacy endpoints included the percent change from baseline in LDL-C and LDL-C response (LDL-C <70 mg/dL [1.8 mmol/L]) at week 52, percent change from baseline in LDL-C and total cholesterol (TC) at week 12, and percent change from baseline at week 52 in TC, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), TC/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low density lipoprotein cholesterol (VLDL-C).
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 and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood. Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
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