Phase 3 Data on Fenfluramine for Lennox-Gastaut Published

Megan Brooks

May 05, 2022

A daily dose of fenfluramine (Fintepla, UCB), when added to an existing anti-epileptic treatment regimen, significantly reduced the frequency of drop seizures associated with Lennox-Gastaut syndrome (LGS) in the phase 3 study that led to US approval.

"Our trial data and the clinical evidence demonstrates the safety and efficacy of Fintepla in LGS, and especially for patients where generalized tonic-clonic seizures are the predominant seizure type, where there is a greater risk of mortality," principal investigator Kelly Knupp, MD, with Children's Hospital Colorado, Aurora, said in a news release.

The study was published online May 2 in JAMA Neurology.

A Challenging Disorder

The trial met its primary efficacy endpoint. Children taking fenfluramine at a dose of 0.7 mg/kg/day had significantly fewer drop seizures than peers taking placebo. The estimated mean between-group difference in drop-seizure frequency was –19.9% (P = .001).

The median percentage reduction in the frequency of drop seizures with fenfluramine 0.7 mg/kg/day was 26.5%, compared to 7.6% with placebo (P = .09).

One quarter of children taking this dose experienced at least a 50% reduction in drop-seizure frequency compared with 10% of children taking placebo.

Site investigators and caregivers gave a much improved or very much improved rating on the Clinical Global Impression of Improvement scale to more patients taking fenfluramine than placebo (26% vs 6%; P = .001).

Generalized tonic-clonic seizures were the subtype that appeared most responsive to fenfluramine, with a decrease in frequency of 45.7%.

The most common adverse reactions in children treated with fenfluramine were decreased appetite (22%), fatigue (13%), and somnolence (33%).

"LGS is a highly treatment-resistant developmental and epileptic encephalopathy and we need differentiated treatment options, such as Fintepla, which has a unique mechanism of action different from and complementary to current antiseizure medications,” Knupp said in the news release.

The study was funded by Zogenix, now part of UCB. Knupp has received grants from Zogenix, Stoke, Encoded Therapeutics, Colorado Department of Public Health, and West Therapeutics; consulting fees from BioMarin, Epygenix, and Biocodex; and other support as a data and safety monitoring board member from Greenwich Pharmaceuticals outside the submitted work.

JAMA Neurol. Published online May 2, 2022. Full text

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