Parting ways with asthma and diabetes

A pair of drug development deals that seemed to many to be promising have been abandoned by Big Pharma players today, with Pfizer returning full rights for allergic asthma therapy R343 to Rigel Pharmaceuticals Inc. and sanofi-aventis walking away from MBX-2982, an orally active GPR119 agonist for the treatment of Type 2 diabetes that it was exploring with Metabolex.

Rigel Pharmaceuticals reports that it will assume development of R343, its inhaled syk inhibitor for allergicasthma that recently completed several Phase I clinical trials, reporting that Pfizer is returning rights because of that company'sdecision to exit the allergy and respiratory therapeutic area withinR&D. Rigel is evaluating the details of R343's development to dateand expects to design a Phase II clinical trial with R343 later thisyear.

"It is rare in our business that one has the opportunityto develop an asset which is both promising and on which the researchand development has been as well done as the package that Pfizer istransferring to us. R343 will now become Rigel's most advanced in-house project," says James M. Gower, chairmanand CEO of Rigel. "The introduction of a therapeutic that would target a possible underlying cause of allergic asthma, suchas R343's inhibition of syk in the immune cascade, may provide asignificant advancement in the treatment of this disorder."

In2005, Rigel licensed to Pfizer its portfolio of inhaled small-molecule sykinhibitors and a year later, Pfizer identified R343 as the leadproduct candidate for intrapulmonary delivery in the potential treatment of allergic asthma. R343 is said to be highly selective to syk and has exhibitedlimited systemic exposure. In 2007, Pfizer began the firstin a series of Phase I clinical trials of R343 in normal healthy adultsand then later in mildly asthmatic adults. The initial results fromthese clinical trials, which have not yet been published, reportedly showed R343 to be well-tolerated and with beneficial improvement in both the early and late phase asthmatic responses following an allergen challenge.

The reasons for sanofi walking away from its collaboration with Metabolex are less clear, but many are speculating that is has much to do with how much larger, more complex and more expensive diabetes trials have become. While the market to treat diabetes is ever-growing and potentially lucrative, the U.S. Food and Drug Administration now requires drug developers to look more closely atpotential cardiovascular risks with regard to diabetes drugs, and that makes the payoff more uncertain for companies.

But the SEC filing by sanofi announcing its decision to walk away says nothing specific, and Metabolex spokesperson Don Hill told the San Francisco Business Times that Phase IIa data revealed no major concerns related to the drug's safetyor efficacy, adding, "We need to assess if we will pursue another trial or partner it outagain."

Sanofi took $47 million "impairmentloss against intangible assets" in the first quarter, mainly related tothe agreement with privately held Metabolex.