Fenfluramine NDA Accepted for Dravet Syndrome

Stephen J. Farr, PhD

The FDA has accepted the new drug application (NDA) for fenfluramine oral solution (Fintepla; Zogenix) for the treatment of seizures associated with Dravet syndrome (DS). In addition, the drug has been granted priority review by the FDA.

The drug has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 25, 2020.

The NDA was supported by results from 2 positive phase 3 trials, as well as an interim analysis from an ongoing open-label extension study, showing that fenfluramine was effective, meeting all primary and secondary endpoints. The study included 232 patients across a 24-month treatment period, and showed that treatment with fenfluramine reduced seizures by 63.9% compared with placebo.

“The FDA’s acceptance for the filing of the NDA under priority review for our investigational product, fintepla, represents a significant milestone in its development,” said Stephen J. Farr, PhD, president and CEO of Zogenix, in a statement. “We are excited to continue working with the FDA with the goal of bringing fintepla to Dravet syndrome patients and their families in need as quickly as possible.”

Zogenix has been informed that although fenfluramine has been granted priority review, the FDA is not currently holding an advisory meeting for the drug. In the meantime, the company anticipates releasing top-line data in the first quarter of 2020 from an ongoing phase 3 trial assessing the efficacy of fenfluramine in patients with Lennox-Gastaut syndrome.

Fenfluramine has been on the FDA track for a while. Zogenix originally filed their NDA in April 2019, only to receive a refusal to file letter from the agency due to some missing and incorrect datasets. The NDA was resubmitted in September 2019 after the company worked with the FDA to clarify the issues identified.

Zogenix also recently presented positive data for the reduction of tonic-clonic (TC) seizures in patients with DS at the 2019 Child Neurology Society Annual Meeting in Charlotte, North Carolina, which took place October 23-26, 2019.

The randomized, placebo-controlled studies included 206 patients (55% male; mean age, 9) and evaluated 3 different doses, 0.2 mg/kg/day (n=39), 0.5 mg/kg/day (n=43), and 0.8 mg/kg/day (n=40), compared with placebo (n=84). Fenfluramine was administered as adjunctive treatment to current antiepileptic drug regimens.

The median baseline monthly frequency of generalized TC seizures ranged from 8.0 to 12.3/month in the 4 dose groups. Each decreased by 80%, 64%, and 48% in the fenfluramine 0.8, 0.5, 0.2 mg/kg/day groups, respectively, compared with 10% in the placebo group.

Focal-to-bilateral TC seizures were experienced by fewer patients, with a median baseline frequency of 2.0 to 4.7/month. During treatment, median percent reductions in focal-to-bilateral TC seizure frequency were 97%, 33%, and 69% in the fenfluramine 0.8, 0.5, 0.2 mg/kg/day groups, respectively, compared with a 39% reduction in the placebo group.

REFERENCE

Zogenix announces FDA acceptance for filing of new drug application and priority review for fintepla for the treatment of dravet syndrome [news release]. Emeryville, CA: Zogenix. November 25, 2019. globenewswire.com/news-release/2019/11/25/1951951/0/en/Zogenix-Announces-FDA-Acceptance-for-Filing-of-New-Drug-Application-and-Priority-Review-for-FINTEPLA-for-the-Treatment-of-Dravet-Syndrome.html. Accessed: November 25, 2019.