FDA Refuses to Review Zogenix Seizure Drug, Says File Not Complete

Xconomy San Francisco — 

[Updated 9:11 p.m. ET. See below.] The FDA is refusing to review a Zogenix drug developed to treat seizures caused by a rare form of epilepsy.

Zogenix said Monday that the FDA sent the company a “refusal to file” letter regarding its drug, fenfluramine hydrochloride (Fintepla). Such letters don’t amount to a rejection of a drug. But they do inform drug companies about deficiencies spotted by the FDA’s initial review of a submission, and the letter tells the company what it must do to address them.

Shares of Emeryville, CA-based Zogenix (NASDAQ: ZGNX) sank more than 31 percent to $35.55 in after-hours trading.

The FDA flagged two problems, Zogenix says. First, the company did not submit certain non-clinical studies to allow the FDA to assess chronic administration of the drug. The second problem is an incorrect version of a clinical dataset, which prevented the regulator from completing its review. Zogenix says the FDA has not asked for more clinical data showing efficacy, nor did it request additional studies to demonstrate the drug’s safety.

Zogenix developed its drug to treat seizures caused by Dravet syndrome, a rare form of epilepsy. The Zogenix drug, a liquid solution, is a low-dose formulation of the appetite suppressant fenfluramine. The compound is the “fen” part of the “fen-phen” weight loss combination drug that was withdrawn from the US market in the 1990s due to cardiovascular risks. In clinical trials, Zogenix did not report any such side effects.

[The following two paragraphs added with analyst comments.] In a research note, Stifel analyst Paul Matteis wrote that the FDA’s refusal to file letter is “legitimately puzzling.” He noted that more than 200 Dravet patients have been treated with the Zogenix drug for up to one year, and the company is currently conducting a separate study in Lennox-Gastaut syndrome, another form of epilepsy. Matteis added that this research includes an open-label extension study, and “you’d think that the FDA would have asked for, or been comfortable with, prior preclinical toxicology studies before signing off on the conduct of extension trials.”

Zogenix filed for FDA approval under the 505(b)2 pathway, which allows a company to rely on safety and efficacy data from previous researchers. But Matteis noted that those data are from the 1960s and ’70s. If Zogenix needs to conduct more preclinical toxicology research, the company’s filing could be delayed by 12 to 15 months. Nonetheless, based on the efficacy and safety data of the drug from clinical trials, as well as the few treatment options for Dravet patients, Matteis views FDA approval of the drug as “very likely.”

If Zogenix is able to steer its drug to approval, it would compete against cannabidiol (Epidiolex), a GW Pharmaceuticals (NASDAQ: GWPH) drug that last year became the first FDA-approved therapy for Dravet syndrome.

Zogenix says it plans to seek a meeting with the FDA to clarify the problems and respond to the agency.