Sanofi reported that its investigational GLP-1 agonist, Lyxumia (lixisenatide), in combination with Lantus (insulin glargine) achieved its primary efficacy endpoint of significantly reducing HbA1c, with a significant improvement in post-prandial glucose, in the GetGoal Duo 1 study (also known as EFC10781).
Positive topline results of GetGoal Duo1 demonstrated the efficacy and safety of lixisenatide in combination with insulin glargine in patients with type 2 diabetes uncontrolled on oral anti-diabetics (OADs) – mainly metformin.
This randomized, double-blind, placebo-controlled study included a 12-week run-in period with insulin glargine initiated and titrated to reach a target fasting plasma glucose of 80-100 mg/dL followed by a 24-week randomized period where 446 patients with HbA1c >7% - despite controlled fasting plasma glucose - received either lixisenatide once-daily or placebo while insulin glargine and metformin were continued. 88% of patients in the lixisenatide arm reached and remained on the 20 µg maintenance dose.
During the run-in period, HbA1c decreased on average from 8.60% to 7.60%. After randomization the addition of lixisenatide led to a further significantly greater HbA1c decrease compared with placebo (p<0.0001) to a mean value of 6.96% after 24 weeks with a significantly higher percentage of patients achieving target HbA1c <7.0% with lixisenatide vs. placebo (56.3% vs. 38.5%, respectively, p=0.0001).
Lixisenatide also significantly improved 2-h post-prandial glucose with a mean difference of -3.16 mmol/L (p<0.0001) vs placebo. The mean difference in change in body weight between the lixisenatide and placebo groups was -0.89 kg (p=0.0012).
Consistent with the GLP-1 class, the most common adverse events were mild and transient nausea and vomiting. Fifty (22.4%) lixisenatide-treated patients and 30 (13.5%) patients in the placebo group reported symptomatic hypoglycemic events as defined in the protocol during the on-treatment period.
“Lixisenatide is a promising new GLP-1 agonist with a mode of action which complements that of basal insulin. Added once-daily to optimally titrated Lantus, it safely improved HbA1c with beneficial effects on both post-prandial glucose and body weight,” commented Dr. Matthew Riddle, Professor of Medicine and Head of the Diabetes Division at the Oregon Health and Science University, Portland, US.
''This is another key milestone in the clinical development program for our new GLP-1 agonist,” declared Pierre Chancel, Senior Vice-President of Sanofi Diabetes. “Achieving glycemic control and compliance with treatment is a complex challenge. These positive results show that once-daily lixisenatide in combination with Lantus could be an innovative therapeutic option for the treatment of uncontrolled type 2 diabetes by addressing its pathophysiology especially regarding post-prandial glucose control with a convenient once-daily regimen, helping those patients who fail to meet HbA1c target despite controlled fasting plasma glucose."
On November 16th, 2011 the European Medicines Agency (EMA) accepted Sanofi’s marketing authorization application filed for Lyxumia (lixisenatide). Submission for regulatory approval of lixisenatide in the U.S. is expected in Q4 2012.
The full study results from GetGoal Duo 1 are planned to be presented at a future medical congress.
Lixisenatide, a glucagon-like peptide-1 agonist (GLP-1), is in development for the treatment of patients with type 2 diabetes mellitus. Lixisenatide was in-licensed from Zealand Pharma A/S (Copenhagen, Denmark), www.zealandpharma.com. Lyxumia® is the intended trademark of lixisenatide. Lixisenatide is not currently approved or licensed anywhere in the world.
GLP-1 is a naturally-occurring peptide that is released within minutes of eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate insulin secretion by pancreatic beta cells. GLP-1 receptor agonists are in development as an add-on treatment for type 2 diabetes and their use is endorsed by the European Association for the Study of Diabetes, the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology.