Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Bedaquilin (neues anwendungsgebiet: multiresistente pulmonale tuberkulose, 12 bis < 18 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: Bedaquiline is approved as part of a combination therapy (background therapy=BR) for pulmonary multi-drug resistant tuberculosis (MDR-TB) in adolescent subjects (12-18 years, weight at least 30kg) based on an evidence transfer of the RCT C208 (conducted in adults) to the patient population assessed in the study C211. The evidence transfer was not followed because no patient-relevant endpoints for a transferability were available, small sample size (N=15) of study C211 and shorter duration (interim data until week 24) compared with study C208 (study duration 120 weeks) and due to limitations in the comparability of patient populations and disease symptomatology. The benefit assessment was based on interim data (data cut point: November 14, 2017) from the pivotal study C211, a single-arm multi-center phase II study (24-week treatment phase with bedaquiline +BR 24-weeks treatment phase and a 96-week follow-up phase (BR only)) in patients with confirmed or probable MDR-TB. The risk of bias was considered high due to the single-arm study design. The results of the endpoint culture conversion were presented for data cut off at week 24 as a supplement despite unclear patient relevance, as the endpoint is considered an important criterion for healing. Six of 8 patient with confirmed MDR-TB and MGIT-eligible samples met the requirements for the endpoint at the end of week 24. The number of subjects with adverse events (AE) was comparable for the treatment phase and part of follow-up (median observation period of 42 weeks (min; max: 20; 78)). AE occurred in 93.3% of subjects, severe AE in approximately 26.7%, serious AE in 13.3% and AE of special interest in 33.3%. No AE resulted in discontinuation of bedaquiline therapy, but BR medications had to be discontinued in 33.3% of subjects. Results for a longer observation period were not presented, so a comprehensive assessment of the long-term effects of treatment cannot be conclusively made at this time.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/520/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4418/2020-08-20_AM-RL-XII_Bedaquiline_D-520_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/520/#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/