Efficacy of Fenfluramine in Reducing Generalized Tonic-Clonic Seizures: Kelly Knupp, MD

WATCH TIME: 5 minutes

"Across the studies, 29% of patients who responded had a 100% response rate for generalized tonic-clonic seizures, which is really quite striking."

Developmental and epileptic encephalopathies (DEEs) are recognized as pharmacoresistant seizures and developmental delay. Patients living with DEEs typically have multiple seizure types, such as tonic–clonic seizures (TCS), which can be generalized tonic–clonic (GTCS) or focal evolving to bilateral tonic–clonic (FBTCS). Prior studies show that fenfluramine (Fintepla; UCB), an FDA-approved antiseizure medication, displayed efficacy in reduction of TCS in patients with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and other DEEs.

A recent meta-analysis published in Epilepsia showed that fenfluramine treatment resulted in improvements in GTCS or TCS frequency regardless of the DEE evaluated.^1,2 Using the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Review Guidelines (PRISMA-ScR), the literature search, conducted through February 2023, identified 422 records, of which 14 were included in the review. Of these, 9 included patients with DS, 1 with CDKL5 deficiency disorder, 1 SCN8A-related disorder, 1 LGS, 1 SCN1B-related disorder, and 1 with other DEEs.

The median percent reduction in GTCS or TCS from baseline was available in 10 studies (n = 328) and ranged from 47.2% to 100%. In the 4 non-DS publications specifically, the median percent reduction in GTCS or TCS from baseline ranged from 48.8% to 100% in 115 patients. In the three DS randomized controlled trials, median percent reductions in GTCS ranged from 47.2% to 90.8%. In the other DS publications, which consisted of case reports or open-label studies, the median reductions reported were 75.0%, 74.5%, and 100%.

Coauthor Kelly Knupp, MD, pediatric epileptologist at Children's Hospital Colorado, sat down with NeurologyLive^® in an interview to discuss the types of studies that were included in the review. Knupp, who also serves as a pediatric neurologist, and associate professor of pediatrics and neurology at University of Colorado, talked about how effective fenfluramine was in reducing generalized tonic-clonic seizures, citing data from the review. Furthermore, she spoke about the importance of considering individual variability when prescribing fenfluramine to patients in this seizure population.

REFERENCES
1. FINTEPLA® (fenfluramine) Results Examining its Impact in Managing Generalized Tonic-Clonic Seizures in Developmental and Epileptic Encephalopathies Published in Epilepsia. News release. June 24, 2024. Accessed July 12, 2024. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/FINTEPLA-fenfluramine-results-examining-its-impact-in-managing-generalized-tonic-clonic-seizures-in-developmental-and-epileptic-encephalopathies-published-in-epilepsia
2. Nagel AG, Cross HJ, Devinsky O, et al. Comprehensive scoping review of fenfluramine’s role in managing generalize tonic-clonic seizures in developmental and epileptic encephalopathies. Epilepsia. Published online June 21, 2024. doi:10.1111/epi.18020