Original Title: Arzneimittel-Richtlinie/Anlage XII: Ataluren – Ablauf Befristung

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: Ataluren was authorised by the EMA in 2014 on the basis of a placebo-controlled, double-blind Phase 2b study with the aim of improving walking ability compared to placebo based on the 6-minute walking distance (6MWD) and was assessed by the G-BA when it entered the German market. In a decision dated 21 May 2015, the extent of the added benefit for this indication was determined to be "minor" and the decision was simultaneously limited until 1 June 2016. With regard to the evidence to be provided, the EMA requested that the results of an ongoing Phase 3 trial in the indication be submitted (PTC124-GD-020-DMD trial). The results of this trial form the basis of this benefit assessment. This is a multicentre, randomised, placebo-controlled, double-blind phase 3 study in a parallel group design (1:1) with two treatment arms. The study included a 2-week screening phase, a 48-week blinded treatment phase and a 6-week follow-up phase. Male patients aged ≥7 years to ≤16 years with clinical symptoms typical of DMD, elevated creatine kinase and problems with walking that manifested at 6 years of age were included. Primary endpoint was the 6MWD. A total of 230 patients with an average age of 9 years were randomised. The potential for bias at study level was estimated to be low The absolute difference in the primary endpoint (6MWD) was not significant (12.98m; 95%-CI -7.44;33.39, p=0,213). During the course of the study, 23 patients (9 in the Ataluren group and 14 in the placebo group) lost their ability to walk. 19 of these patients had a walking distance in the 6MWD of <300 metres at baseline; the remaining 4 patients were in the placebo arm in the group with ≥300 to <400 metres walking distance. In the subgroup of patients with a baseline walking distance of ≥300 to <400 metres, a statistically significant and clinically relevant effect of around 44 metres was shown both in the current phase 3 study and in the meta-analysis with the approval-relevant phase IIb study, but the lower confidence interval was below the relevance threshold in each case. The number of adverse events was comparable between the treatment groups. Treatment discontinuations due to adverse events occurred in one patient per group. No deaths occurred during the study period.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/239/#english

Year Published: 2016

URL for published report: https://www.g-ba.de/downloads/39-1464-2773/2016-12-01_AM-RL-XII_Ataluren_D-239_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/239/#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/