Sanofi announces results from Phase IIIb ELIXA study of Lyxumia in adults with diabetes and high CV risk

Sanofi announced today the presentation of full results of the Phase IIIb ELIXA study, which was designed to assess the cardiovascular (CV) safety of Lyxumia^® (lixisenatide) in adults with type 2 diabetes and high CV risk. As previously reported, lixisenatide met the pre-specified criterion of non-inferiority versus placebo for the composite primary endpoint of CV death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for unstable angina but did not demonstrate superiority. The full results will be included in the U.S. New Drug Application for lixisenatide, which is on track to be resubmitted to the U.S. Food and Drug Administration in Q3 2015.

Additional safety findings include no signal for increased risk of heart failure, pancreatitis, pancreatic cancer or severe symptomatic hypoglycemia. Lixisenatide was generally safe and well tolerated; nausea and emesis (vomiting), which are known side effects of the GLP-1 RA class, were observed more frequently with lixisenatide.

"The importance of determining the CV safety of diabetes medicines, as set out in the FDA guidance issued in 2008, is widely recognized. People around the world are being treated with GLP-1 receptor agonists, and the CV effects were unknown," said Dr. Marc Pfeffer, Professor of Medicine at Harvard Medical School, Senior Physician in the Division of Cardiovascular Medicine at Brigham and Women's Hospital and Chair of the ELIXA Steering Committee. "ELIXA goes beyond the FDA guidance to deliver data related to heart failure and other insights that are not currently available for any other GLP-1 receptor agonist. Our data provide the medical community, patients and caregivers with information that will better inform them about how lixisenatide can be safely used to better control their glucose."

"As the first completed long-term CV safety study of a GLP-1 receptor agonist, the successful ELIXA trial will be shared with health authorities around the world and provides important outcomes data that can be considered by healthcare professionals," said Pierre Chancel, Senior Vice President, Head of Global Diabetes at Sanofi. "Sanofi is committed to developing and delivering safe and effective treatment options for people with diabetes. This study supports that important work."

Full study results were presented today during a symposium at the American Diabetes Association 75th Scientific Sessions in Boston.

Results of Analysis
Lixisenatide met the pre-specified criterion of non-inferiority versus placebo for the composite primary endpoint of MACE⁺: CV death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for unstable angina (Hazard Ratio [95% CI]: 1.017 [0.886 to 1.168]). Since the upper bound of the 95% CI was greater than 1.0, superiority over placebo in reducing the composite primary endpoint was not met.

The CV safety of lixisenatide was also confirmed by further analyses (e.g. MACE Hazard Ratio [95% CI]: 1.02 [0.887 to 1.172]). No signal for increased risk of heart failure (HF) was observed (Hazard Ratio [95% CI]: 0.96 [0.75 to 1.23]).

Measures of non-CV safety showed pancreatitis (0.2% with lixisenatide and 0.3% with placebo), pancreatic cancer (<0.1% with lixisenatide and 0.3% with placebo), severe symptomatic hypoglycemia (0.3 events per 100 patient-years with lixisenatide; 0.6 per 100 patient-years with placebo), malignancy (2.9% with lixisenatide and 2.6% with placebo), drug-related allergic reactions (0.2% with both lixisenatide and placebo).