Sometimes the Bear Gets You: Idenix Pharmaceuticals Edition

Idenix Pharmaceuticals announced this morning that FDA had placed a clinical hold on its Phase II valopicitabine hepatitis C polymerase inhibitor.

FDA made its decision following an assessment of the overall risk benefit profile observed in clinical rials to date, according to Idenix CEO JP Sommadossi, who addressed analysts on a conference call today. "We were very surprised," he said, adding that along with its partner Novartis, Idenix is evaluating its options. "But i am not optimistic about further development of valopicitabine in the future," Sommadossi added, and later re-emphasized.

So what happened? "FDA looked at all of the Phase IIB data ... and concluded that the GI side effect profile was not commensurate with the antiviral activity we were seeing," said Doug Mayers, CMO. Idenix, the executives said, had seen similar signals such as nausea and vomiting, but were eager to play with the doses of valopicitabine in further trials in an attempt to find a workable risk/benefit profile. FDA had different ideas.

Valopicitabine, previously dubbed NM283, was the furthest-along HCV polymerase inhibitor in clinical development and the first of a next-generation set of targeted HCV therapies. The polymerase class hasn't received as much attention as HCV protease inhibitors, which have been the subject of some pretty sizeable deals--Vertex's alliance with Johnson & Johnson and Intermune's alliance with Roche, for example. But Idenix had maintained that the future of HCV antiviral therapy would be combination, a sentiment shared by many, and so pushed ahead with development despite only moderate clinical success with the compound.

The biotech's partner Novartis must have agreed; the companies have a broad alliance whereby Novartis gets first right of refusal on any Idenix compound when it hits Phase II. For valopicitabine, Novartis had to pony up more than half a billion dollars to maintain its share of the drug. Novartis owns upwards of 57% of Idenix.

Today's news is the second clinical hold placed on a Novartis-in-licensed HCV candidate this year. Last summer FDA halted trials of Anadys' ANA975 drug, a TLR-7 agonist in Phase Ib, after a preclinical toxicology study unearthed a potential safety signal.

HCV dealmaking has definitely been a hot space, and will likely continue to be so despite this spate of clinical difficulties. For our roundup of drugs in development for HCV, see this late-2005 IN VIVO story.

UPDATE: Idenix shares are off about two bucks, or 35%, at about 11:30a.