Press release from Sanofi
ELIXA is the first event-driven cardiovascular outcomes study to provide data for a GLP-1 receptor agonist -
Full results for ELIXA study presented at American Diabetes Association's 75th Scientific Sessions -
Paris, France - June 8, 2015 - 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.
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 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).
ELIXA (Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With Lixisenatide) is the first event-driven cardiovascular outcomes study to provide data for a glucagon-like peptide-1 receptor agonist (GLP-1 RA).
ELIXA was a randomized, double-blind, parallel group trial designed to evaluate cardiovascular risk, comparing lixisenatide to placebo in a high-risk population of adults with type 2 diabetes. More than 6,000 adults with type 2 diabetes and high CV risk (i.e., patients who have recently experienced a spontaneous acute coronary syndrome event) participated in the trial. The composite primary endpoint, which was evaluated for non-inferiority and superiority, comprised cardiovascular (CV) death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for unstable angina. The global ELIXA study started in June 2010 and was completed in 2015.
Lixisenatide is a once-daily prandial glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of adult patients with type 2 diabetes mellitus. GLP-1 is a naturally-occurring peptide hormone that is released within minutes after eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate glucose-dependent insulin secretion by pancreatic beta cells.
From Nyhetsinfo www DiabetologNytt
ADA Report. First CVD Outcome Trial of a GLP-1 Agonist
No Cardiac Risk or Benefit
Popular Glucose-Lowering Drugs Also Show No Risk of Hypoglycemia or Pancreatic Injury, and Modest Benefit for Weight Compared to Placebo
One member of a widely prescribed class of drugs used to lower blood glucose levels in people with diabetes has a neutral effect on heart failure and other cardiovascular problems, according to the first clinical trial to examine cardiovascular safety in a GLP-1 receptor agonist, presented at the American Diabetes Association’s 75th Scientific Sessions.
The Evaluation of GLP1-analog Lixisenatide in Acute Coronary Syndrome (ELIXA) study also found a modest benefit for weight control, and no increase of risk for hypoglycemia or pancreatic injury in those who took lixisenatide, one of several GLP-1 receptor agonists being prescribed around the world to treat people with type 2 diabetes. GLP- 1 receptor agonists are derived from gut hormones and may be used as a secondary therapy when other medications fail to sufficiently lower blood glucose levels.
“There has been a cloud of suspicion over all new diabetes drugs, including GLP-1 agonists, over whether they may increase the risk for cardiovascular problems,” said Marc Pfeffer, MD, PhD, Dzau Professor of Medicine at Harvard Medical, Senior Physician in Cardiology at Brigham and Women’s Hospital and Principal Investigator for the ELIXA trial.
“There has also been some hope that some of these drugs may improve cardiovascular health. GLP-1 receptor agonists were being used around the world while CVD safety had yet to be established.
This is the first report of a clinical trial designed to assess cardiovascular outcomes in this class of drugs and we have shown that patients and their healthcare providers should have no cause for concern, even if they are at high risk for heart-related problems.”
Specifically, the ELIXA study found no increased risk for cardiovascular death, heart attack, stroke, unstable angina (chest pain) or heart failure in people with type 2 diabetes who had recently experienced acute coronary syndrome events (an umbrella term referring to when blood supplied to the heart muscle is suddenly blocked) and were therefore at high risk for additional heart problems. The study examined 6,068 people from 49 countries, randomly assigning them to lixisenatide or placebo, with a follow-up period of more than two years.
Heart disease and stroke are the number one causes of death and disability among people with type 2 diabetes, who are two to four times more likely than those who do not have diabetes to suffer from these conditions. Because of this, the U.S. Food and Drug Administration has recently augmented cardiovascular surveillance for new drugs prescribed to treat elevated blood glucose in patients with type 2 diabetes, including
GLP-1 receptor agonists.
The ELIXA trial also showed that those who took lixisenatide were not more likely to have problems with hypoglycemia (low blood glucose) than those who took placebo, despite better blood glucose control.
“Knowing these drugs can be prescribed safely gives physicians another tool to further lower glucose without producing more hypoglycemia, a potential complication of improved glycemic control,” said Eldrin Lewis, MD MPH, Associate Professor of Medicine, Harvard Medical School, Advanced Heart Disease section of Cardiovascular Division at Brigham and Women’s Hospital. “These drugs can provide a very important adjunct to therapy. We want to get people to target to minimize the future consequences of diabetes, but we don’t want to add any additional risks in doing so.”
The ELIXA trial also found no increase in pancreatitis or cancers and a modest benefit in terms of weight gain, said Matthew Riddle, MD, Professor of Medicine, in the Division of Endocrinology, Diabetes, & Clinical Nutrition, at Oregon Health & Science University. Those taking lixisenatide did not gain weight, while those taking placebo did.
Those taking lixisenatide did, however, report a higher number of episodes of nausea and vomiting, common side effects for GLP-1 receptor agonists. “Nausea and vomiting sometimes caused patients to discontinue the medication,” said Riddle, “but in terms of serious reactions or pancreatic problems, there was no difference between the two groups and no increased risk.”
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