Infinity Pharma back under a cloud after duvelisib disappoints in PhII

Three years after it was forced to restructure the company in the wake of the failure of its then lead drug, Infinity Pharmaceuticals ($INFI) finds itself in a new crisis. The Cambridge, MA-based biotech says that its lead drug duvelisib hit the primary endpoint in a Phase II study for indolent non-Hodgkin lymphoma but fell short of expectations, forcing the company to pause work on a combo with AbbVie and shutter its discovery efforts to save cash.

The news crushed the biotech's share price Tuesday morning, plunging 66% in pre-market trading.

Investigators for the 15-year-old company say that their dual PI3-K delta/gamma inhibitor rang up an overall response rate of 46% in the study--all partial--which wasn’t competitive enough to excite anyone involved in the study. And that is costing the jobs of 46 staffers in the discovery group, 21% of the company’s staff.

The latest setback is also spurring a re-think of the collaboration between AbbVie and Infinity. The partners are pausing an AbbVie-run Phase Ib/II study pairing duvelisib with venetoclax as they “explore next steps for the parties' collaboration.” And Infinity is also jerking its financial guidance as it regroups.

“While the DYNAMO study met its primary endpoint, we hoped that treatment with duvelisib as a monotherapy would have provided a larger clinical benefit for patients with advanced indolent non-Hodgkin lymphoma, a difficult-to-treat disease," said Adelene Perkins, president and chief executive officer at Infinity, in a statement. "We plan to seek feedback from the U.S. Food and Drug Administration to determine our next steps with respect to duvelisib in indolent non-Hodgkin lymphoma.”

"From a competitive perspective, Zydelig previously showed an ORR of 58% and Rituxan itself showed 48%-57%, so duvelisib’s lack of differentiation does not appear to support a strong case for a filing later this year absent strong data from the Phase 3 DUO study," noted Barclay's Geoff Meacham. "With regard to the duvelisib partnership with AbbVie, we believe that the low ORR and likely unfavorable survival metrics put the viability of the duvelisib monotherapy and Venclexta/duvelisib combination programs into further doubt though no formal announcement has been made as discussions remain ongoing."

"This why drug development tough in indolent #lymphoma 46% ORR gets this reaction," tweeted Dr. John Leonard, a noted investigator at Weill Cornell. But picking out the ways in which the drug fell short of expectations is difficult with nothing but the press release to go on, he adds. 

“Hard to say much from press release only,” Leonard noted in a direct message. “Not sure why this is disappointing or what "bar" was targeted especially since it is said to have "met primary endpoint.” As described it is basically what I would have expected. It also seems to be in ballpark of efficacy of idelalisib and relative toxicity would also be of interest.”

Almost all of Infinity’s eggs are in one basket for duvelisib. The biotech has 7 ongoing studies in the pipeline with 1 early-stage effort for IPI-549 in solid tumors.

Infinity was forced to restructure in the summer of 2012 after the failure of its then lead program for saridegib, raising considerable doubts about its gung-ho approach to drug development. And that key setback followed the biotech's first big clinical disaster in 2009. But AbbVie, which has been steadily upping the ante in oncology, stepped in in 2014 with a $275 million upfront to partner on duvelisib.

- here's the release