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.1
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 percent in evolocumab) were nasopharyngitis, upper respiratory tract infection, influenza and back pain.
"Data from the Phase 3 DESCARTES study of evolocumab add to the promising safety and efficacy data we recently saw in the MENDEL-2 study and 52-week Phase 2 OSLER study," said Sean E. Harper, M.D., executive vice president of Research and Development at
Details of the DESCARTES study results will be submitted to a future medical conference and for publication.
According to the
DESCARTES Study Design
DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) is a Phase 3 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
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).
The Phase 3 program includes 13 trials, with a combined planned enrollment of more than 28,000 patients. The Phase 3 studies will evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2), in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2), as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2), and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia.
Five studies of evolocumab will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease, DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease, and GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization.
Additional information about clinical trials of evolocumab can be found at www.clinicaltrials.gov.
Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).1 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.5 Evolocumab, being developed by
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1. Amgen Data on File, Investigator Brochure.
2. CDC Morbidity and Mortality Weekly Report.
5. Abifadel M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.