Original Title: Arzneimittel-Richtlinie/Anlage XII: Cannabidiol (Neubewertung nach Fristablauf: Dravet-Syndrom, ≥ 2 Jahre, Kombination mit Clobazam)

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: Cannabidiol (Epidyolex®) is used in addition with clobazam, in patients two years of age and older for the adjuvant treatment of seizures associated with Dravet syndrome (DS). The benefit assessment of cannabidiol is based on the pivotal studies GWEP1424 (GWPCARE2) and GWEP1332 part B (GWPCARE1). Both studies are randomized, double-blind, placebo-controlled, multicentre phase III studies and investigated the efficacy and safety of cannabidiol as an adjunctive antiepileptic treatment vs. placebo in children and adolescents (2 to 18 years) with DS. The study population was based on a subpopulation and included 127 (GWEP1424) and 78 (GWEP1332 part B) participants randomized in a 2:2:1:1 and a 1:1 ratio, respectively, and stratified by age group in study GWEP1332. Treatment duration lasted 14 weeks. Post hoc meta-analyses were performed for the 20 mg dose of the two studies. There were no deaths in the studies. Cannabidiol showed statistically significant advantages over placebo in convulsive seizures with unclear potential for bias. No differences occurred between study arms in the frequency of nonconvulsive seizures. Episodes of status epilepticus occurred only rarely in both studies. Assessment of Global Caregiver Impression of Change showed improvement with cannabidiol compared to placebo although highly biased. No statistically significant differences occurred between study arms in epilepsy-rated hospitalizations. However, uncertainties remain as the data were adjusted post hoc. Quality of life, measured by the QOLCE, showed no relevant difference between treatment arms. Study GWEP1424 showed no significant differences between treatment arms regarding the evaluation of safety. Study GWEP1332 part B showed a significant difference in severe adverse events (AE) to the disadvantage of cannabidiol (20mg/kg/day). Results of the meta-analysis were not statistically significant. At the level of AE by SOCs and PTs, there were multiple statistically significant differences between treatment arms to the detriment of cannabidiol. Under the treatment of cannabidiol 20 mg/kg/day, statistically significantly more patients discontinued the study due to an AE.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/600/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4789/2021-04-15_AM-RL-XII_Cannabidiol%28Dravet%29_D-595_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/600/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

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/