Positive data from Lyxumia study on type 2 diabetes presented at ADA 2011

Sanofi (EURONEXT: SAN and NYSE: SNY) announced today data from four studies  of its once-daily GLP-1 receptor agonist Lyxumia® (lixisenatide) that  is in Phase III clinical development, including data that demonstrates positive results in type 2 diabetes patients not at goal on oral therapies or with  basal insulin. These data are being presented or published at the American Diabetes Association's 71st Scientific Sessions in San Diego, California.

"Efficacy and Safety of Lixisenatide Once-Daily Versus Exenatide Twice-Daily in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-X)" [ABSTRACT 0033-LB]

"Lixisenatide once daily demonstrated efficacy in blood glucose control by meeting an endpoint of non-inferiority  at week 24 in a head-to-head study versus exenatide twice daily," said Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center at Medical City Dallas and lead investigator of the GetGoal-X trial.

In the GetGoal-X trial, a randomized, open-label, active-controlled, two-arm parallel-group, multicenter study with a 24-week main treatment period, lixisenatide once daily achieved its primary endpoint of non-inferiority in A1C reduction from baseline with less symptomatic hypoglycemia (low blood sugar) and better gastrointestinal tolerability versus exenatide twice daily, as an add-on to metformin in patients with type 2 diabetes. A total of 634 people were randomized to receive either lixisenatide or exenatide. Both groups received a stepwise increase in dose, up to a maximum daily dose of 20 microgram.  At baseline, the mean age in the trial was 57.4 years, mean diabetes duration 6.8 years, mean body mass index (BMI) 33.6 kg/m2 and mean A1C 8.0 percent.

Key Findings:

• Lixisenatide once daily achieved its primary endpoint of  non-inferiority in A1C reduction versus exenatide twice daily (LS mean +/- SE change from baseline: -0.79 +/- 0.05 vs. -0.96 +/- 0.05)
• Improvements in mean fasting plasma glucose – measurement of blood glucose levels when a patient is fasting – (LS mean +/- SE change from baseline: -22.0 +/- 2.1 vs. -26.1 +/- 2.1) and the percentage of patients achieving the study target A1C < 7.0 percent (48.5% vs. 49.8%) were comparable between groups
• Mean body weight significantly decreased from baseline in the lixisenatide group compared to the exenatide group (94.5 to 91.7 kg with lixisenatide vs. 96.7 to 92.9 kg with exenatide)
• The proportion of patients with serious adverse events was generally comparable between groups
• Discontinuations due to adverse events (mainly gastrointestinal events including nausea, diarrhea and vomiting) were 33 (10.4%) in the lixisenatide group and 41 (13.0%) in the exenatide group
• Significantly fewer patients experienced symptomatic hypoglycemia with lixisenatide (2.5% vs. 7.9%, p<0.05), with 6-fold fewer hypoglycemic events (8 vs. 48) versus exenatide
• More lixisenatide patients tolerated the target dose of 20 microgram per day and completed the trial versus the exenatide 10 mcg target dose (93% vs. 83%)

"Lixisenatide  Significantly  Improves  Glycemic  Control  in  Asian  Patients   with  Type  2 Diabetes Insufficiently Controlled on Basal Insulin +/- Sulfonylurea" [ABSTRACT 0278-OR]

Data from the GetGoal-L Asia trial, showed in  Asian patients with type 2 diabetes insufficiently controlled by basal insulin +/- sulfonylurea, that lixisenatide once daily significantly improved glycemic control (as  measured by the number of patients reaching  a target A1C < 6.5 percent or < 7.0 percent) versus placebo at week 24 with a pronounced post-prandial glucose and fasting plasma glucose effect, and was well tolerated.

Key Findings:

• Lixisenatide once daily significantly improved A1C versus placebo (LS mean difference -0.9%)
• Significantly more lixisenatide patients achieved A1C less than or equal to 6.5 percent (17.8%) and <7.0 percent (35.6%) versus placebo (1.3% and 5.2%; p<0.0001)
• Lixisenatide significantly improved two-hour  post-prandial  glucose, glucose excursion and average  7-point  self-measured  plasma  glucose  (SMPG)  over  placebo  (LS  mean  +/-  SE change from baseline: 7.96 +/- 0.598 vs. -0.14 +/- 0.563, p<0.0001; -7.09 +/- 0.576 vs. 0.14 +/- 0.542, p<0.0001; -1.91 +/- 0.272 vs. -0.56 +/- 0.271, p<0.0001, respectively)
• Lixisenatide  was  well  tolerated  and  86  percent  of  patients  in  the  lixisenatide  group completed the study versus 92 percent on placebo
• Nine placebo patients (5.7%) and ten lixisenatide patients  (6.5%) experienced a serious treatment emergent adverse event and more lixisenatide patients (14 [9.1%]) discontinued participation in the study due to treatment emergent adverse events than placebo patients (5 [3.2%]), mainly due to gastrointestinal adverse events
• As expected in an insulin +/- sulfonylurea-treated population, the percentage of patients with symptomatic hypoglycemia was higher with lixisenatide (42.9%) versus placebo (23.6%); the rate decreased to 31.8 percent versus 28.3 percent in those not receiving sulfonylurea
• There were no cases of severe hypoglycemia

"Cardioprotective Effect of the GLP-1 Receptor Agonist Lixisenatide on Ischemia- Reperfusion-Induced Injury in the Isolated Rat Heart" [ABSTRACT 0968-P]

In this pre-clinical study, data showed that lixisenatide once daily protects against myocardial ischemia-reperfusion injury (tissue damage caused by restriction of oxygen rich blood to the heart) in isolated rat hearts by significantly reducing myocardial infarct size (measurement of damage to the heart) in the isolated rat heart model.

Key Findings:

• Administration of lixisenatide at 0.3 nM starting ten minutes prior to and during reperfusion significantly reduced myocardial infarct-size by 36 percent>
• The observed cardioprotective effect was not associated with a significant change in cardiac hemodynamics (mechanisms involved in circulation), particularly coronary flow, suggesting a direct cardiac effect

"Effect of the Once-Daily GLP-1 Receptor  Agonist Lixisenatide on Gastric Emptying  and Prandial  Carbohydrate  Utilization  in  Animal  Models:  A  Comparison   with  Liraglutide" [ABSTRACT 2267-PO]

Data from several animal studies showed that  treatment with lixisenatide was more effective in delaying   gastric   emptying   and   lowering   prandial   glucose   excursions   (change   in   glucose concentration after a meal) than liraglutide.

Key Findings:

• Lixisenatide  strongly  and  dose-dependently  inhibited  gastric  emptying  in  rats  with  a significant emptying effect already present at 1 microgram/kg sc
• Even a 100 times higher dose of  liraglutide was ineffective and significant inhibition of gastric emptying was observed only at doses of 500 microgram/kg and above
• In an oral glucose tolerance test in dogs, 1 microgram/kg sc lixisenatide almost completely abolished blood glucose excursion
• With  liraglutide,  the  glucose-lowering  effect  during  oral  glucose  tolerance  testing  was significantly weaker than that of lixisenatide, even when liraglutide was administered at 50-100 times higher doses
• After administration of  a liquid meal, lixisenatide (3 microgram/kg sc) given  to mice was more effective in lowering prandial glucose excursions than liraglutide (200 microgram/kg) and lixisenatide (10 microgram/kg) injected subcutaneously to diabetic mice improved glucose tolerance at least as effectively as liraglutide (200 microgram/kg sc)