Original Title: Arzneimittel-Richtlinie/Anlage XII: Pitolisant (Neues Anwendungsgebiet: Narkolepsie, mit oder ohne Kataplexie, (Kinder und Jugendliche, 6 - 17 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: Pitolisant is approved for the treatment of narcolepsy with/without cataplexy in patients ≥6 years. The current benefit assessment is based on market extension for patients 6-18 years old and of the pivotal study P11-06, a double-blind, multicenter, randomized, placebo-controlled study followed by an open treatment phase to investigate the safety and efficacy of pitolisant in children (age: 6-18 years) with narcolepsy with/without cataplexy. Randomization was stratified by study center in a 2:1 ratio into the intervention (Pitolisant: N=72) or control arm (placebo: N=38). The final results of the double-blind study phase of in total 9 weeks (treatment period 8 weeks) were considered for the assessment (data cut-off: Nov 15th, 2021). No deaths were observed during the 9-weeks period. For the endpoint Clinical Global Impression of Change - Excessive Daytime Sleepiness (CGI-C EDS), a statistically significant advantage for Pitolisant over placebo was observed (RR: 1.62; [95% CI: 1.03; 2.55]; p-value: 0.016) but not for other endpoints (CGI-C cataplexy, Children's Depression Inventory (CDI) 2 – short version, Columbia Suicide Severity Rating Scale (C-SSRS)). Overall, the number of adverse events (AE) were comparable between both treatment arms. Only for the AE “Infections and infestations” a statistically significant advantage for Pitolisant compared to placebo was observed (RR: 0.22 [0.06; 0.79], p-value: not available). Only, 2 severe AE were observed in the intervention- and none in the placebo-arm. No serious AE or AE leading to discontinuation of study treatment were observed. Overall, only for efficacy endpoint CGI-C EDS, an advantage for Pitolisant over placebo was observed. AE frequency was low in both treatment arms. Uncertainties remain due to the short study duration and specifically for the endpoint CGI-C cataplexy, as analysis was performed on patients with cataplexy at baseline only (85% of the intervention- and 76% of the control arm).

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/938/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6167/2023_09_21_AM-RL-XII_Pitolisant_D-916_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/938/#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/