Sanofi snaffles novel diabetes drug


It has been a momentous few months for Metabolex. The licensing of MBX-2982, one of the leading phase II candidates from a novel class of anti-diabetic agents, to Sanofi-Aventis today for up to $375m follows a pre-clinical stage deal with Johnson & Johnson earlier this week for $330m and a research collaboration with Takeda in April for the private company.

MBX-2982 is a GPR119 receptor agonist (or G-protein coupled receptor 119) which affects both insulin and glucagon-like peptide-1 (GLP-1) release. This novel class of drug has suddenly hit the headlines, Neurocrine Biosciences and Boehringer Ingelheim struck a deal last week to discover new GPR119 agonists, and before Sanofi’s deal today Metabolex’s candidate was the only unpartnered clinical stage GPR119 asset (see table below). The likes of Swedish Orphan Biovitrum, Exelixis, LG Life Sciences and Kalypsys could therefore see increased partnering interest in their pre-clinical and research stage GPR119 assets.

Novel approach

GPR119 is a receptor in the gut and pancreas that interacts with bioactive lipids to stimulate glucose-dependent incretin and insulin secretion. Orally delivered agonists of GPR119 potentially have a dual mechanism of action, by stimulating both pancreatic beta cells to increase insulin secretion and the release of incretin GLP-1 from the intestines.

Proponents of the class therefore claim that GPR119 agonists will offer improved glucose level control over existing diabetic agents, with further potentially beneficial effects on weight and the health of pancreatic islet beta cells.

Leading the way

As the table below shows MBX-2982 and GlaxoSmithKline’s 1292263 (or GSK1292263) are leading the class of GPR119 agonists.

Pipeline of G-protein coupled receptor GPR119/ glucose-dependent insulinotropic receptor (GDIR) agonist
Status Product Company Originator
Phase II MBX-2982 Metabolex/Sanofi-Aventis Metabolex
1292263 GlaxoSmithKline GlaxoSmithKline
Phase I APD597 Arena Pharmaceuticals/Johnson & Johnson Arena Pharmaceuticals
PSN821 Astellas Pharma/Lundbeck Lundbeck
Pre-clinical GPR119 Agonists Bristol-Myers Squibb Bristol-Myers Squibb
GPR 119 Project Swedish Orphan Biovitrum Swedish Orphan Biovitrum
GPR119 Follow-on Metabolex/Sanofi-Aventis Metabolex
Research project GPR119 Agonists Neurocrine Biosciences/Boehringer Ingelheim Neurocrine Biosciences
GPR119 Exelixis Exelixis
GPR119 Agonist LG Life Sciences LG Life Sciences
PSN821 Backup (AS1535907) Astellas Pharma OSI Pharmaceuticals
GPR119 Research Program Kalypsys Kalypsys

Data: EvaluatePharma

Detailed phase I data from both candidates will be presented at the American Diabetes Association (ADA) conference starting today; given the recent headline-grabbing deals for products in this class these presentations and data from related research are likely to attract heightened interest.

The phase II trial of MBX-2982 compares the drug against placebo and sitagliptin, Merck & Co’s DPP-IV inhibitor, Januvia. According to the study is due to complete in September so results may be released in the fourth quarter this year.

Meanwhile the phase II trial of 1292263, also up against placebo and sitagliptin, completed in March this year, so results could be imminent. Data from both trials of MBX-2982 and 1292263 will certainly be critical in assessing not only the chances of these specific drugs achieving regulatory and commercial success but also the class of GPR119 agonists as a whole.

Slim partnering pickings

What the table of pipeline candidates also shows is that the majority of GPR119 agonists are either already partnered or in the hands of a big pharma company.

For example, both phase I candidates are unlikely to need a partner to help extend development. Arena Pharmaceuticals licensed APD597 to J&J in 2004 when the candidate was still in pre-clinical studies, while Astellas Pharma recently got its hands on PSN821 through its acquisition of OSI Pharmaceuticals.

Therefore a company wanting to get in on the GPR119 scene will have to start their own research from scratch or make a move on the handful of smaller biotech companies that are already some way down the development track, albeit mainly still at the pre-clinical stage.

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