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).2 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.8 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 high cholesterol on risk-based lipid-lowering therapy

Therapeutic area: Cardiovascular diseases

Country:

Trial details:

• MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy For Easing Lipid Levels-2) is a Phase 3 randomized, multicenter, double-blind, double-dummy, placebo- and ezetimibe-controlled parallel group study designed to evaluate the efficacy and safety of evolocumab in 614 hyperlipidemic patients with a 10-year Framingham risk score of 10 percent or less who were not receiving lipid-lowering therapy. Patients were randomized to one of six treatment groups to compare two dosing regimens of evolocumab (140 mg every two weeks or 420 mg monthly) with placebo and ezetimibe (10 mg daily). The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; 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 and data from MENDEL-2, the monotherapy study, were simultaneously published in the Journal of the American College of Cardiology .
• The MENDEL-2 study showed that in 614 patients with high cholesterol (LDL-C =100 mg/dL and

  Results of the study showed the mean percent reduction from baseline in LDL-C at weeks 10 and 12 were 57 percent for evolocumab 140 mg every two weeks and 57 percent for evolocumab 420 mg monthly compared to placebo; and 39 percent for evolocumab 140 mg every two weeks and 40 percent for evolocumab 420 mg monthly compared to ezetimibe.

  At week 12, the percent reduction from baseline in LDL-C was 57 percent for evolocumab 140 mg every two weeks and 55 percent for evolocumab 420 mg monthly compared to placebo; and 39 percent for evolocumab 140 mg every two weeks and 38 percent for evolocumab 420 mg monthly compared to ezetimibe.

  The most common AEs (=2 percent in evolocumab combined group) were headache (3.3 percent evolocumab; 3.2 percent ezetimibe; 2.6 percent placebo), diarrhea (2.9 percent evolocumab; 1.9 percent ezetimibe; 3.9 percent placebo), nausea (2.6 percent evolocumab; 1.9 percent ezetimibe; 0.6 percent placebo) and urinary tract infection (2.3 percent evolocumab; 1.9 percent ezetimibe; 1.3 percent placebo).

Is general: Yes