Sanofi announced that Lyxumia (lixisenatide), a once-daily GLP-1 receptor agonist under development for type 2 diabetes, achieved its primary efficacy endpoint of significant HbA1c reduction vs. placebo in patients uncontrolled on metformin. The study objectives were to compare the efficacy and safety of lixisenatide versus placebo in one-step and two-step dose increase regimens in terms of reduction in HbA1c.

“Efficacy and Safety of Lixisenatide Once-Daily Versus Placebo in Patients with Type 2 Diabetes Insufficiently Controlled on Metformin (GetGoal-F1)” [ABSTRACT 784]

The GetGoal-F1 trial, one of nine studies in the GetGoal clinical programme, was a randomized, double-blind, placebo-controlled, parallel group, multi-centre study with a 24-week main treatment period. A total of 482 people with type 2 diabetes were randomized and exposed to one of the following once-daily regimens: lixisenatide one-step dose increase (10µg for two weeks, then 20µg); lixisenatide two-step dose increase (10µg for one week, 15µg for one week, then 20µg), or placebo, as add on to metformin.

Top-line results show that lixisenatide significantly reduces HbA1c from baseline to week 24 in both treatment regimens, compared with placebo (one-step: -0.92%; two-step: -0.83% vs. placebo: -0.42%; p<0.0001). The percentage of patients reaching HbA1c targets of = 6.5% and HbA1c < 7.0% with the one-step regimen was 25.6% and 47.4% and with the two-step regimen was 20.4% and 42.1% versus 7.6% and 24.1% with placebo, respectively.

In addition, both one- and two-step regimens reduced body weight: one-step: -2.63kg; two-step: -2.68kg versus placebo: -1.63kg; (p-value 1-step = 0.0042; p-value 2-step = 0.0025).

“The GetGoal-F1 study shows that, in people with type 2 diabetes not achieving adequate glycemic control, lixisenatide once daily as ‘add on’ to metformin is effective in both improving glycemic control and reducing body weight, and the one-step dose increase regimen may be the best option for treatment initiation,” said Geremia Bolli, MD, of the University of Perugia, Italy and lead investigator of the GetGoal-F1 study.

The percentage of patients who discontinued during the main 24-week treatment period due to adverse events was 5.6 percent in the one-step regimen, 8.1 percent in the two-step regimen versus 2.5 percent with placebo. Overall, lixisenatide was well tolerated and gastrointestinal event levels were as expected for the GLP-1 class. The most frequently reported adverse events were nausea (26.1% [1-step], 35.4% [2-step] vs. 4.4% with placebo) and vomiting (11.8% [1-step], 15.5% [2-step] vs. 0% with placebo). There was no increased risk of severe hypoglycaemia.

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). Lyxumia is the intended trademark for 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.

The GetGoal phase III clinical programme will provide data for lixisenatide in adults with type 2 diabetes treated with various oral anti-diabetic agents or insulin. With nine trials in the program, GetGoal started in May 2008 and has enrolled more than 4,300 patients. To date, GetGoal-X, GetGoal-L, GetGoal-L Asia, GetGoal-Mono and GetGoal-S have reported positive top-line results supporting efficacy and safety for lixisenatide. Further results are expected during 2011.

Sanofi strives to help people manage the complex challenge of diabetes by delivering innovative, integrated and personalized solutions. Driven by valuable insight that comes from listening to and engaging with people living with diabetes, the Company is forming partnerships to offer diagnostics, therapies, services, and devices. Sanofi markets both injectable and oral medications for people with type 1 or type 2 diabetes. Investigational compounds in the pipeline include an injectable GLP-1 agonist being studied as a single agent, in combination with basal insulins, and/or in combination with oral antidiabetic agents.

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