fenfluramine in Lennox-Gastaut syndrome

Last edited 11/2022 and last reviewed 01/2023

Fenfluramine in Lennox-Gastaut syndrome

Lennox-Gastaut syndrome (LGS)

• is a developmental and epileptic encephalopathy characterized by multiple seizure types (most notably, tonic seizures, approximately 56%), accompanied by an abnormal electroencephalogram with diffuse slow spike-and-wave complexes at <3 Hz, and cognitive impairment, leading to life-long disability (1)

Fenfluramine (FFA), a serotonergic medication

• is an amphetamine derivative and racemic mixture of D- and L-enantiomers
• was used in France as an antidepressant and then soon after for weight loss in 1963 (2)
• has been successfully repurposed, and various regulatory agencies approved it for seizures associated with Dravet and Lennox-Gastaut syndromes (2)

Fenfluramine in Lennox-Gastaut syndrome

• in open-label extension (n=247), patients experienced reduced drop and non-drop seizure frequencies (median 28.6% and 45.9%) during treatment with fenfluramine at a median treatment duration of 364 days
• reduced drop and nondrop seizure frequencies (median=28.6% and 45.9%)
• reduced frequency of generalized tonic-clonic seizures by a median of 48.8%
• resulted in 75 of 241 patients (31.1%) with >=50% reduction in drop seizure frequency
• was equally tolerable and effective in adult and pediatric patients
• was well tolerated, with no pulmonary arterial hypertension or valvular heart diseas
• at about 1 year (n = 170), reduction in drop seizure frequency was 51.8%

Reference:

• Knupp KG, Scheffer IE, Ceulemans B, Sullivan J, Nickels KC, Lagae L, Guerrini R, Zuberi SM, Nabbout R, Riney K, Agarwal A, Lock M, Dai D, Farfel GM, Galer BS, Gammaitoni AR, Polega S, Davis R, Gil-Nagel A. Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: Interim analysis of an open-label extension study. Epilepsia. 2022 Oct 5. doi: 10.1111/epi.17431.
• Samanta D. Fenfluramine: A Review of Pharmacology, Clinical Efficacy, and Safety in Epilepsy. Children (Basel). 2022 Aug 2;9(8):1159.