FDA Accepts sNDA, Grants Priority Review to Fenfluramine for Lennox-Gastaut Syndrome

Gail Farfel, PhD

According to a new announcement, the FDA has accepted for filing and granted priority review designation to Zogenix’s fenfluramine (Fintepla) to treat seizures associated with Lennox-Gastaut syndrome (LGS). The FDA will look to complete the review within the 6-month window, with a prescription user drug fee act (PDUFA) date of March 25, 2022.¹

The application, submitted in September 2021, was backed by data from the phase 3 Study 1601 (NCT03355209), which showed that treatment with fenfluramine at a dose of 0.7 mg/kg/day was superior to placebo in reducing the monthly drop seizure frequency (MDSF; P = .0012). Additional long-term safety and effectiveness data in ongoing open-label extension trials were also included in the submission.

"This is a critically important milestone for our FINTEPLA development program in LGS and brings us one step closer to a potential new treatment option for this rare and difficult to treat childhood developmental and epileptic encephalopathy,” Gail Farfel, PhD, executive vice president and chief development officer, Zogenix, said in a statement.¹ "We look forward to working closely with the FDA to potentially bring FINTEPLA for the treatment of seizures associated with LGS to market as quickly as possible."

READ MORE: Investigational Dravet Syndrome Agent STK-001 Demonstrates Safety in Phase 1/2a

If approved, this would be the second indication for fenfluramine, after originally being greenlight by the FDA in June 2020 to treat seizures associated with Dravet syndrome in patients 2 years of age and older.

In total, those in Study 1601 who were treated with fenfluramine 0.7 mg/kg/day achieved a –19.9% estimated median difference (ESM) from placebo in MDSF from baseline, which was comparable to the magnitude demonstrated in all other completed LGS randomized controlled trials (range, –14.8% to –21.6%).²

The same dose group also showed statistically significant improvements compared with placebo on several secondary efficacy end points. This included the proportion of patients with a clinically meaningful reduction, defined as at least 50% in drop seizure frequency, which occurred in 25.3% of patients on fenfluramine compared with 10.3% on placebo (P = .0165).

Overall, the therapy’s safety profile was well-tolerated and similar to what had been previously observed in studies of DS. The incidence of patients experiencing an adverse event was 89.7% in the 0.7 mg/kg/day group, 76.4% in the 0.2 mg/kg/day group, and 79.3% in the placebo group.

Although the ESM in MDSF from baseline in the cohort of patients treated with fenfluramine 0.2 mg/kg/day (n = 89) did not reach statistical significance (–10.5%; P = .09), investigators and caregivers rated patients “much improved” or “very much improved” on clinical global impression of improvement (CGI-I) for both doses compared with placebo. Tonic-clonic seizures, which were documented in 43% of the patient population, were reduced by 45.7% (P = .007) and 58.2% (P <.0001) with treatment of fenfluramine 0.7 mg/kg and 0.2 mg/kg per day, respectively.

REFERENCES

1. Zogenix announces US FDA acceptance for priority review of supplemental new drug application for fintepla (fenfluramine) for the treatment of seizures associated with Lennox-Gastaut syndrome. News release. Zogenix. December 1, 2021. Accessed December 1, 2021. https://finance.yahoo.com/news/zogenix-announces-u-fda-acceptance-130000785.html

2. Knupp K, Sullivan J, Nickels K, et al. Efficacy and safety of fintepla (fenfluramine) for the treatment of seizures associated with Lennox-Gastaut syndrome: a randomized, double-blind, placebo-controlled clinical trial. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 852.