Date: 2016-03-02
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in The New English Journal of Medicine
Company: Regeneron Pharmaceuticals (USA - NY) Geisinger Health System (USA - PA)
Product:
Action mechanism:
Disease: coronary artery disease
Therapeutic area: Cardiovascular diseases
Country:
Trial details:
Latest
news: * On March 2, 2016, Regeneron Pharmaceuticals, working in collaboration with Geisinger Health System, announced that the New England Journal of Medicine has published a paper showing that inactivating mutations of the angiopoeitin-like 4 (ANGPTL4) gene are associated with a significantly reduced risk of coronary artery disease (CAD) in humans. ANGPTL4 inhibits lipoprotein lipase (LPL), an enzyme that helps break down triglycerides, a form of fat derived from food. Previous studies have found that activation of LPL leads to the reduction of circulating triglycerides, increased levels of which are thought to be an independent risk factor for ischemic cardiovascular disease. It was hypothesized, therefore, that genetic mutations inactivating ANGPTL4 would lead to activation of LPL, low levels of circulating triglycerides and reduced risk of cardiovascular disease. In this study, scientists at the Regeneron Genetics Center sequenced the exomes of individuals in the DiscovEHR cohort, comprised of de-identified Geisinger Health System patients who consented to participate in the MyCode Community Health Initiative. Analyses revealed that individuals with one or two copies of the p.E40K mutation, which was previously known to inactivate ANGPTL4, had about 19 percent lower CAD risk. People with one of 13 other ANGPTL4 "loss-of-function" mutations newly-identified by the researchers had an almost 45 percent reduction in CAD risk. Further evaluation is needed to characterize the potential efficacy and safety of ANGPTL4 inhibition in humans. Regeneron currently has an angiopoeitin-like 3 (ANGPTL3) antibody, known as evinacumab or REGN1500, in clinical development. ANGPTL4 and ANGPTL3 are thought to be related inhibitors of LPL. ("Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease". Dewey FE and al.N Engl J Med. 2016 Mar 24;374(12):1123-33. doi: 10.1056/NEJMoa1510926. Epub 2016 Mar 2.)
