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

The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)
Record ID 32018002140
English, German
Original Title: Arzneimittel-Richtlinie/Anlage XII: Fenfluramin (Dravet-Syndrom, ≥ 2 Jahre)
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: Fintepla is indicated for the treatment of seizures associated with Dravet syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older. The benefit assessment is based on the pivotal studies ZX008-1501 and ZX008-1502 (collectively referred to as study 1) and ZX008-1504 (study 1504). Study 1501 and Study 1502 were multicentre, randomised, placebo-controlled, double-blind, parallel-group phase III studies. Study 1 was a pooled presentation of the first recruited participants from study 1501 (n=72) and study 1502 (n=47). Study 1504 is a multicentre, randomised, placebo-controlled, double-blind, phase III study. All studies assessed children and adolescents aged 2-18 years with Dravet syndrome. The study populations included 119 and 115 patients randomised in a 1:1:1 (Fintepla 0.2 mg/kg/day vs. Fintepla 0.7 mg/kg/day or 0.4 mg/kg/day for participants with concomitant stiripentol in Study 1502 vs. placebo) and 1:1 ratio (Fintepla 0.4 mg/kg/day vs. placebo) for study 1 and study 1504, respectively. Randomisation was stratified for age (< 6 vs. ≥ 6 years). Medication was given as add-on therapy to existing anti-epileptic therapy. Primary endpoint was the change in the frequency of convulsive seizures. No deaths occurred in the study courses. Results showed homogenous statistically significant advantages for Fintepla over control group in the number of convulsive seizures and in the Clinical Global Impression of Change (CGI-C). Heterogenous results were seen for Fintepla vs. control group in the assessment of quality of life (PedsQL). Overall, more AE occurred in the intervention vs. control arm in study 1. In contrast, study 1504 showed only small percentage differences at this level. In both studies, differences for the preferred term "appetite decreased" emerged to the disadvantage of Fintepla. Only few severe AEs occurred in both studies, which were numerically more frequent in the intervention arm.
Project Status: Completed
Year Published: 2021
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
  • Child
  • Infant
  • Epilepsies, Myoclonic
  • Anticonvulsants
  • Fenfluramine
  • Seizures
  • Spasms, Infantile
  • Fenfluramine
  • 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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