Fenfluramine Shows Safety, Efficacy in Seizure Reduction in Lennox-Gastaut Syndrome

Presenting at the 2022 AAN Annual Meeting, researchers investigated the long-term efficacy of fenfluramine in patients with LGS.

The following article is part of conference coverage from the 2022 American Academy of Neurology (AAN) Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the 2022 AAN Annual Meeting.


Treatment with fenfluramine led to a reduction in drop seizure frequency among patients with Lennox-Gastaut syndrome (LGS), according to study results presented at the 2022 American Academy of Neurology (AAN) Annual Meeting, held from April 2 to April 7 in Seattle, Washington, and virtually from April 24-26, 2022.

Drop seizure is a seizure causing a sudden loss of muscle strength possibly leading to a collapse that is frequently experienced by patients with LGS, a type of epilepsy which has proven difficult to treat. Illness, multiple seizure types, and death are also associated with LGS. Prior research has found patients with LGS treated with fenfluramine 0.7 mg/kg/day showed a significant reduction in drop seizures compared to placebo (median 26.5% vs 7.6%; P =.0013).

The objective of the current study was to investigate the long-term efficacy of fenfluramine in patients with LGS.

The researchers conducted an open-label extension (ClinicalTrials.gov Identifier: NCT03355209) that enrolled 247 patients (mean 14.3±7.6 years of age [79 {32%} adults 18 years of age or older]) who had completed the 14-week phase 3 randomized clinical trial. All patients in the open-label extension began with 0.2 mg/kg/day and after 1 month, medication levels were adjusted individually, then patients were reevaluated at 3-month intervals for effectiveness and tolerability.

Patients were also treated with additional antiseizure medications (ASM) not being tested, with most patients receiving 2-4 ASMs. Researchers found that at month 3 there was a 39.4% median decrease in monthly frequency of drop seizures, and that reduction was maintained through 12 months (51.8%). In the final months of the trial, 87 patients experienced a reduction in drop frequency equal to or greater than 50%, and half of the researchers and caregivers declared significant improvement in patients. Decreased appetite (16.2%) and fatigue (13.4%) were noted as the most frequent adverse consequences to the medication. No patients reported valvular heart disease (VHD) or pulmonary arterial hypertension (PAH).

Researchers concluded, “Patients with LGS experienced sustained (39.4%-51.8%) reduction in drop seizure frequency during fenfluramine treatment from 3-12 months… Fenfluramine may provide an important new treatment option for LGS.”

Fenfluramine showed few side-effects and was not associated with VHD or PAH.


Knupp K, Scheffer I, Ceulemans B, et al. Interim analysis of long-term safety and efficacy of FINTEPLA (fenfluramine) in patients with Lennox-Gastaut syndrome. Presented at: the 2022 AAN Annual Meeting; April 2-7, 2022; Seattle, Washington; April 24-26, 2022; Virtual Meeting. Abstract S13.010.