- An unexpected regulatory misunderstanding could push back the approval timeline for Zogenix's only drug candidate by up to 15 months, sending shares in the California biotech down 27% at market open Tuesday.
- Zogenix had submitted an application to the Food and Drug Administration for approval of Fintepla in February. But last Friday the regulator notified the biotech it wouldn't begin review of the drug, citing two problems with the application — a development that Zogenix disclosed Monday afternoon.
- One issue flagged by the FDA was inclusion of an incorrect data table, an error by Zogenix that it expects to fix easily. Yet the other could result in a significant delay of more than a year: the company never ran certain non-clinical toxicology studies that the FDA says are required for its review. "This requirement is definitely unexpected for us," CEO Stephen Farr told investors and analysts on a Monday conference call.
Zogenix has requested a meeting with the FDA to discuss the letter and develop a re-submission plan. Until then, Farr provided few concrete answers for Wall Street analysts on how the letter will affect the timeline of Fintepla (fenfluramine hydrochloride).
The critical question facing Zogenix is whether the FDA will require the company to start the missing toxicology studies from scratch. If so, Farr expected that to push back approval by 12 to 15 months. This misunderstanding, Farr said, came out of differing assumptions about the filing's requirements.
But the chief executive sees a way around that, hoping that old, historical preclinical data on fenfluramine will suffice.
Paul Matteis, an analyst at Stifel, was left scratching his head over the FDA's decision, calling it "legitimately puzzling" in a note to investors. Matteis questioned why the agency was OK with human testing of Fintepla, including open-label extension trials, given this preclinical data gap.
Matteis said the previous preclinical toxicity studies were done in the 1960s and 1970s on fenfluramine, and he voiced uncertainty if that would be sufficient for the FDA given methodology changes since then.
The safety concerns from the agency could hold elevated importance given fenfluramine's history. The drug was approved in 1973 for short-term use as an appetite suppressant, but was also widely used in an off-label combination with phentermine as an obesity treatment, dubbed Fen-Phen. The drug was withdrawn from the U.S. market in 1997 after reports of cardiovascular issues, including primary pulmonary hypertension.
More than two decades since that withdrawal, Zogenix has tested the drug as a treatment for two rare types of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. The application now in question was for Dravet syndrome.
Zogenix was already playing catch-up to GW Pharmaceuticals, which snagged the FDA's OK last year for those two severe conditions. After launching on Nov. 1, GW's Epidiolex (cannabidiol) has beaten Wall Street sales expectations in its first months on the market. GW's stock rose 2% Tuesday over the news of Zogenix's delay.
European regulators have already accepted Fintepla's application, with a regulatory decision expected in the first quarter of 2020. Farr said he didn't expect these issues to impact the European application, nor does he expect it to impact the Lennox-Gaustat clinical program, saying it "continues as planned."