Sanofi-Aventis' 10-trial, 4,000-plus patient Phase III program for lixisenatide, a glucagon-like peptide 1 agonist for type 2 diabetes, is starting to show results, as the French pharma announced the medicine dosed in combination with a basal insulin significantly improved glycemic control, while presenting no unexpected safety concerns.

It's the second positive announcement in less than two weeks concerning lixisenatide, a molecule whose success is not just critical for Sanofi's nascent diabetes business, but also for the growth of the drug maker overall.

During a same-day business update in Paris, Jochen Maas, VP of research and development, diabetes division, noted that this is big news for the company, as it portends a lucrative future for selling Sanofi's first GLP1 product with its top-seller, Lantus (insulin glargine).

While the GETGOAL-L ASIA study involved administering the two drugs separately in what Sanofi calls a "free combination," company researchers are working on developing a drug/device combination product that will deliver the two drugs in a single injection, Maas explained.

The trial enrolled 311 Asian patients with type 2 diabetes insufficiently controlled with basal insulin. The 24-week study dosed 20 mcg of lixisenatide or placebo along with basal insulin in patients with baseline HbA1c levels of between 7% and 10%. Of the participants, 60% already were taking Lantus.

Mean HbA1c Change Of 0.77% From Baseline

The study met its primary endpoint as treatment-arm patients showed a mean HbA1c change of 0.77%, while placebo arm patients saw their levels increase by a mean change of 0.11%. Lixisenatide also demonstrated postprandial glucose level reductions and a favorable gastrointestinal tolerability profile, as previously seen in the drug's Phase IIb program.

"[These results were] really very exciting because this is a result of lixisenatide given the first time on top of insulin," Maas said. "We found a decrease of HbA1c versus placebo that was close to 0.9% and this is really a tremendous result on top of an insulin. And ... we also have an [indication] of what it means on top of Lantus because 60% of these patients were already on Lantus."

Full data from the trial will be detailed at the American Diabetes Association conference next year in San Diego, he added. Another finding from the top-line data was that lixisenatide demonstrated that many patients could decrease their insulin doses when undergoing combination therapy, he said.

During the European Association for the Study of Diabetes meeting in Sweden Sept. 20, Sanofi had unveiled its first Phase III results for the drug, showing that lixisenatide monotherapy significantly reduced HbA1c levels compared to placebo, while also producing a significant reduction in mean change from baseline in PPG two hours after eating.

The 10 GETGOAL trials are fully enrolled, with all expected to produce final data in 2010 or 2011, Maas said. All involve lixisenatide 20 mcg being dosed once-daily for 24 weeks. Another trial in the U.S. and Europe also is testing the drug with basal insulin, with data expected next year.

Amylin's Byetta (exenatide) was the first GLP1 for diabetes to reach the market, and was joined by Novo Nordisk's Victoza (liraglutide) earlier this year. Along with partners Eli Lilly and Alkermes, Amylin is awaiting FDA approval of a long-acting exenatide formulation (Bydureon), which has an Oct. 22 PDUFA date.

New Diabetes Unit Makes Five Deals This Year

Since launching its diabetes unit earlier this year, Sanofi has increased its focus on the disease, aiming to become an end-to-end solutions provider providing devices along with drugs in an effort to develop a more payor-friendly business model (Also see "Personalizing Patient Care:Sanofi Recasts Its Diabetes Efforts" - In Vivo, 1 July, 2010.). Part of this effort has included inking five different partnerships over a six-month period, highlighted by a tie-up with AgaMatrix to co-develop blood glucose monitoring devices.

Combining lixisenatide with Lantus to further the insulin's franchise is crucial because Lantus is the sole top earner at Sanofi immune from near-term generic competition. Despite being a mature product, sales of Lantus, the industry's top-selling insulin product, increased 11% during the first quarter of 2010.

To get lixisenatide off to a strong start, Maas said, Sanofi recently began a 6,000-patient cardiovascular safety study, with a goal of launching its drug as the first GLP1 agonist with a cardiovascular safety claim. Sanofi also is testing lixisenatide head-to-head with exenatide.

The regulatory plan is to file submissions for lixisenatide in the EU and Japan in the second half of next year, with an FDA filing to follow in second-half 2012. The pharma hopes to have a pen administration device ready to be included with the U.S. filing.

In preparing for launch, Sanofi already has a 9 million-patient market in mind for the lixisenatide/Lantus combination. "We think we have an excellent candidate for patients after the failure of oral anti-diabetic treatment and also for patients as an add-on to a basal insulin," Maas said.

Sanofi projects that between the U.S. and the five largest EU markets, there are approximately 5 million type 2 diabetes patients who have failed to control their disease with OADs, about 2 million who are undercontrolled or not controlled on a GLP1 agonist and will benefit from adding Lantus to therapy, and about 2.2 million Lantus takers who would benefit from lixisenatide's PPG control effect, he explained.

-Joseph Haas (j.haas@elsevier.com)

Sanofi's Lixisenatide/Lantus Combo Could Be A Critical Growth Driver

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