Clinical Trials

Date: 2014-03-29

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The New English Journal of Medicine

Company: Amgen (USA - CA)

Product: evolocumab (AMG 145)

Action mechanism:

• monoclonal antibody/RNAi/PCSK9 inhibitor. 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.

Disease: patients with hyperlipidemia at risk for cardiovascular disease

Therapeutic area: Cardiovascular diseases

Country:

Trial details:

• 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 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 absolute change from baseline in LDL-C and LDL-C response (LDL-C
• PROFICIO , which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.
  The Phase 3 program includes 14 trials to evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2 and YUKAWA-2); in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2 and GAUSS-3); as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2); in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2 and TAUSSIG) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia; as well as the administration of evolocumab (THOMAS-1 and THOMAS-2).

Latest news:

• • On March 29, 2014, Amgen has announced new detailed data from three Phase 3 studies that showed treatment with its novel investigational cholesterol-lowering medication, evolocumab (AMG 145), resulted in a statistically significant reduction of 55-66 percent in low-density lipoprotein cholesterol (LDL-C) compared to placebo in patients with high cholesterol. Results from the three separate Phase 3 studies, MENDEL-2, DESCARTES and RUTHERFORD-2, were presented  as Featured Clinical Research in a Special Session at the American College of Cardiology's 63rd Annual Scientific Session (ACC.14). Data from DESCARTES, the long-term safety and efficacy study, were simultaneously published in the New England Journal of Medicine
• The DESCARTES study showed that in 901 patients with high LDL-C and a range of cardiovascular risk, evolocumab 420 mg subcutaneous monthly reduced mean LDL-C by 57 percent from baseline at week 52 compared to placebo (p<0.001). LDL-C reduction for evolocumab at week 12 was consistent with the long-term efficacy at week 52. Compared to placebo, the mean percent LDL-C reductions from baseline with evolocumab at week 52 are 56 percent, 62 percent, 57 percent and 49 percent in diet alone, atorvastatin 10 mg, atorvastatin 80 mg, and atorvastatin 80 mg plus ezetimibe 10 mg groups, respectively.
• The most common AEs (>5 percent in evolocumab) were nasopharyngitis (10.5 percent evolocumab; 9.6 percent placebo), upper respiratory tract infection (9.3 percent evolocumab; 6.3 percent placebo), influenza (7.5 percent evolocumab; 6.3 percent placebo) and back pain (6.2 percent evolocumab; 5.6 percent placebo).

Is general: Yes