Claims Study Highlights Persistence and Reasons for Fenfluramine Use in Lennox-Gastaut Syndrome

In a first-of-its-kind analysis, researchers highlighted the real-world persistence of fenfluramine (Fintepla; UCB), an antiseizure medication, in patients with Lennox-Gastaut syndrome (LGS), a rare epileptic disorder. The retrospective analysis, which used claims from the Komodo U.S. database, showed that 61% of patients were still using the treatment at 12 months, while also identified smaller trends and reasons behind continued fenfluramine use.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta, Georgia, the study included 373 patients with FFA claims and 2361 without, gathering patient data from 2021 to 2024. Led by Wesley Kerr, MD, PhD, an epileptologist and assistant professor of neurology and bioinformatics at the University of Pittsburgh, the analysis included patients who had at least 1 prescription claim, at least 2 LGS claims, at least 3 months of pre-FFA initiation, and at least 6 months of post-FFA initiation claims data.

Using 544 patients with LGS who had 6- and 12-month persistence data, 73% of patients were still on fenfluramine at month 6 and 61% by month 12. While the study collected data on demographic and clinical characteristics, there were no significant differences between those who had 12-month persistence with fenfluramine (n = 148) and those who dropped off or considered nonpersistent (n = 216).

Although there were no significant differences in demographic or characteristics, the study did find that patients on the antiseizure medication tended to be younger, lived in more socioeconomically disadvantaged neighborhoods, and had a greater disease severity, including a greater number of previously attempted ASMs (5.7 vs 3.7; P <.01), compared with patients not on fenfluramine. Notably, when comparing those who did (n = 373) and did not (n = 2361) receive fenfluramine, there was significantly higher comorbidity burden in the pre-index period.

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In terms of comorbidities, the frequency of these events was as follows: behavioral disorders (FFA claims: 38% vs without: 29%; P <.01), respiratory/cardiovascular complications (69% vs 51%; P <.01), developmental impairments (76% vs 38%; P <.01), gastrointestinal disorders (53% vs 41%; P <.01), mobility dysfunction (36% vs 22%; P <.01), and sleep disturbances (28% vs 16%; P <.01). On comorbidity indexes, investigators recorded scores of 1.5 and 2.3 for the FFA group on Charlson Comorbidity Index and Germaine Smith Index, respectively, compared with scores of 2.0 and 2.8 for those without FFA claims. In addition, those on FFA had significantly higher average area deprivation index (47.7 vs 45.2; P = .03).

Fenfluramine, originally approved for Dravet syndrome, had its indication expanded in 2022 to include the treatment of LGS in children aged 2 years and older. The basis for the approval was 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 monthly drop seizure frequency.^2,3

Since its approval, fenfluramine has continued to be studied in various settings and durations. In addition to LGS and Dravet, the drug has shown some recent success in treating CDKL5 deficiency disorder (CDD), another developmental epileptic encephalopathy. Last year, UCB announced that fenfluramine met its primary end point in the phase 3 GEMZ trial of CDD, with a potential submission in this patient population expected to follow.⁴

Data from GEMZ, also presented at AES 2025, revealed a 47.6% median reduction in CMSF, the primary end point, relative to baseline, compared with 2.8% of those on placebo (P <.001). On the primary end point, the between-group differences translated into a median CMSF reduction of 52.7% (95% CI, –70.0 to –36.7) over the 14-week period. Notably, at the end of the maintenance phase, 45.2% (n = 19) of fenfluramine-treated patients achieved at least a 50% reduction in CMSF, compared with only 4.5% (n = 2) of patients on placebo (P <.001).

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REFERENCES
1. Kerr W, Khushalani J, Henninger H, et al. Fenfluramine Persistence in Patients With Lennox-Gastaut Syndrome: a Retrospective Analysis Using US Claims Data. Presented at: 2025 AES Annual Meeting; December 5-9; Abstract 1.558.
2. FINTEPLA® (fenfluramine) Oral Solution Now FDA Approved for Treatment of Seizures Associated with Lennox-Gastaut Syndrome (LGS). News release. UCB. March 28, 2022. Accessed January 5, 2025. https://finance.yahoo.com/news/fintepla-fenfluramine-oral-solution-now-050000058.html
3.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.
4. Specchio N, March E, Devinsky O, et al. Fenfluramine in CDKL5 Deficiency Disorder: Primary Efficacy and Safety Results From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study. Presented at: 2025 AES Annual Meeting; December 5-9; Atlanta, Georgia. Abstract 2.429