Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: compassionate use program in Germany

  • Objective: Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP). Methods: We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day. Results: Overall, 78 patients with DS (median age = 8.0 years, range = 2.1–46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5 days (range = 31–572). Responder rates (a ≥50% reduction; n = 78) and seizure-freedom rates at 3 months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic–clonic seizures. Responder rates were consistent at 6 and 12 months (n = 66 and n = 43, respectively). Median seizure days per month significantly decreased from 10.0 (range = .5–30) to 3.0 (range = 0–30) in the 3-month period before and after FFA treatment (p < .001). Significantly fewer patients reported at least one episode of status epilepticus (28% vs. 14% patients before and after FFA initiation, p = .005). During FFA treatment, 35 (45%) patients were able to discontinue a concomitant ASM. At the last follow-up date, 66 (85%) patients remained on treatment with FFA. The most common adverse events were somnolence (36%), decreased appetite (22%), and ataxia (8%). Forty-eight (62%) patients were reported as having a meaningful global clinical improvement. Significance: In a large cohort of patients, FFA demonstrated efficacy across a range of outcomes including clinically significant reductions in convulsive seizures, and was well tolerated, providing valuable information for real-world practice. Key Points: Seventy-eight patients with Dravet syndrome were treated with FFA at multiple centers within the CUP in Germany; FFA had a good retention rate over a sustained period; 85% of patients remained on treatment with FFA for a median duration of 255.5 days; FFA was associated with clinically meaningful reductions in total and convulsive seizures, seizure days per month, and episodes of status epilepticus; FFA was associated with reductions in the number or dose of concomitant antiseizure medications in 68% of patients; FFA was well tolerated, with the main adverse events being somnolence (36%), decreased appetite (22%), and ataxia (8%).

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Author:Adam StrzelczykORCiDGND, Milka Pringsheim, Thomas Mayer, Tilman PolsterGND, Kerstin Alexandra Klotz, Hiltrud MuhleORCiDGND, Michael Alber, Regina TrollmannGND, Hartwig Spors, Gerhard Kluger, Gerhard KurlemannGND, Susanne Schubert-BastORCiDGND
URN:urn:nbn:de:hebis:30:3-626752
DOI:https://doi.org/10.1111/epi.17034
ISSN:1528-1167
Parent Title (English):Epilepsia
Publisher:Wiley-Blackwell
Place of publication:Oxford [u.a.]
Document Type:Article
Language:English
Date of Publication (online):2021/08/10
Date of first Publication:2021/08/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/12/20
Tag:Clinical Global Impression of Change; Dravet syndrome; convulsive seizures; fenfluramine; real-world; status epilepticus
Volume:2021
Issue:online version before inclusion in an issue
Page Number:11
First Page:1
Last Page:10
Note:
Early View: Online Version before inclusion in an issue
Note:
This study was supported by a LOEWE grant to A.S. and S.S.-B. from the State of Hessen for the Center for Personalized Translational Epilepsy Research, Goethe University Frankfurt, Frankfurt am Main, Germany. K.A.K. was supported by the Berta Ottenstein Program for Clinician Scientists from the Faculty of Medicine, University of Freiburg, Germany.
Note:
A.S. reports personal fees and grants from Arvelle Therapeutics, Desitin Arzneimittel, Eisai, GW Pharmaceuticals, Marinus Pharma, Medtronic, UCB, and Zogenix. T.M. reports personal fees and grants from Arvelle. Therapeutics, Eisai, GW Pharmaceuticals, UCB, and Zogenix. T.P. reports personal fees and grants from Desitin Arzneimittel, Novartis International, UCB Pharma, and Zogenix International.
Note:
Version of Record: http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:hebis:30:3-645175
HeBIS-PPN:490814239
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0