[Pharmaceutical Directive/Annex XII: Fenfluramine (Dravet syndrome, ≥ 2 years)]

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018004982
English, German
Original Title: Arzneimittel-Richtlinie/Anlage XII: Fenfluramin (Neues Anwendungsgebiet: Lennox-Gastaut-Syndrom, Add-on-Therapie, ≥ 2 Jahren)
Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.
Authors' results and conclusions: Fenfluramine is indicated for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome (LGS) as an add- on therapy to other anti-epileptic medicines for patients 2 years of age and older. The benefit assessment is related to the indication of LGS and the approved dose of 0.7 mg/kg fenfluramine per day. The benefit assessment is based on the pivotal study 1601-part 1. The study 1601-part 1 is a randomized, double-blind, parallel-group, placebo-controlled study to assess the efficacy and safety of 2 dose levels of fenfluramine hydrochloride as adjunctive therapy for seizures in subjects with LGS. 87 patients were randomized to 0.7 mg/kg fenfluramine and placebo, respectively. Epileptic seizures (motor and non-motor seizures), clinical global impression, executive function, suicidal ideation and behaviour, quality of life (QoL) and adverse events are considered as patient relevant endpoints and taken into account for the benefit assessment. Fenfluramine was shown to be superior to placebo in the reduction of motor seizures. These results are associated with a low risk of bias. Statistically significant more subjects achieved an improvement in the clincal global impression in the fenfluramine arm than in the placebo arm (unclear risk of bias). There was no statistically significant difference in the occurrence of non-motor seizures (low risk of bias), the executive function and QoL (both with high risk of bias due to missing data) and the incidence of severe AE, serious AE and treatment discontinuations due to AE between fenfluramine and placebo (low risk of bias). There were no valid data for suicidal ideation and behaviour as a high proportion of patients in both treatment arms did not complete the questionnaires. Conclusions on long-term effects on safety cannot be drawn from this study as comparative data on long-term safety are not available.
Project Status: Completed
Year Published: 2023
Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Germany
MeSH Terms
  • Epilepsies, Myoclonic
  • Lennox Gastaut Syndrome
  • Fenfluramine
  • Seizures
  • Anticonvulsants
  • Fenfluramine
  • Dravet-Sydrome
  • Epilepsies
  • Myoclonic
Organisation Name: The Federal Joint Committee
Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany
Contact Name: Fachberatung Medizin [Department of Medical Consultancy]
Contact Email: Fachberatung-Medizin@g-ba.de
Copyright: https://www.g-ba.de/sys/impressum/
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