Results presented at the American Diabetes Association in June showed no CV risk or benefit and no risk of pancreatic injury, an issue that has been of particular concern to FDA.
FDA has accepted a new drug application (NDA) for Sanofi’s lixisenatide, a GLP-1 receptor agonist, marking the first time that such a filing will include data from a cardiovascular (CV) outcomes trial, the company announced this morning.
Lixisenatide, approved in Europe under the brand name Lyxumia, treats adults with type 2 diabetes has been studied both alone and in combination with Sanofi’s mainstay insulin, Lantus. Today’s NDA announcement is based on results from the GetGoal clinical program, whose results were reported in 2014,1,2 and whose CV results were presented in June at the 75th Scientific Sessions of the American Diabetes Association (ADA).3
Todays’ NDA action is based on 11 multinational, phase 3 clinical trials, in which the main efficacy endpoints were met, with reductions in glycated hemoglobin (A1C) ranging from 0.7% to 1.0%.1 Results from 1 of those trials, reported in Diabetic Medicine in February 2014, found that lixisenatide, given once daily in both one- and two-step dose increases, significantly improved glycated hemoglobin (A1C) at week 24 compared with placebo and allowed more patients to achieve an A1C of < 7.0%.2
What sets lixisenatide apart is the ELIXA trial, presented at ADA, which were the first CV results from the GLP-1 receptor agonist class.3 The trial found that there were no CV benefits or risks from the therapy, which works in the pancreas by suppressing glucagon secretion from the alpha cells and stimulating glucose-dependent insulin by the beta cells. Of note, the ELIXA trial found no risk of pancreatic injury, something that has been of particular concern to FDA.
US regulators have been requiring long-term CV trials for new diabetes and cholesterol medications in the wake of embarrassing events in the prior decade. In one episode, the agency was forced to limit sales of rosiglitazone, after that blockbuster drug was linked to risk of heart attacks in a study in the New England Journal of Medicine. For example, when FDA recently approved the new class of cholesterol medications, the PCSK9 inhibitors, it limited indications while awaiting results of long-term safety trials, which are expected in 2017. Indications in Europe for these same drugs are much broader.
In a statement, Sanofi’s Pierre Chancel, senior vice president and head of Global Diabetes, said, “Sanofi’s integrated portfolio of marketed products provides treatment, monitoring and support at every stage of the diabetes journey. Lixisenatide is a critical element of this portfolio, and we look forward to working with the FDA during the review process with the goal of bringing lixisenatide to patients in the US.”
1. Bain SC. The clinical development program of lixisenatide: a once-daily glucagon-like peptide-1 receptor agonist. Diabetes Ther. 2014;5(2):367-383.
2. Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, Hanefeld M. Efficacy and safety of lixisentaide once daily vs placebo in people with type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014;31(2):176-184.
3. Caffrey MK. ELIXA trial results find no cardiac risk, benefit for lixisenatide. AJMC.com Conference coverage, 75th Scientific Sessions of the American Diabetes Association. ww.ajmc.com/conferences/ADA2015/elixa-trial-results-find-no-cardiac-risk-benefit-for-lixisenatide. Published June 9, 2015. Accessed September 29, 2015.