Original Title: Arzneimittel-Richtlinie/Anlage XII: Bedaquilin (Neubewertung nach Fristablauf: Multiresistente pulmonale Tuberkulose)

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 (Sirturo®) is indicated for the treatment of paediatric and adult patients as part of a combination therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) when an effective treatment regimen cannot be established due to resistance or intolerance. The benefit assessment is based on the pivotal study TMC207-C208 (study C208), a double-blind, randomised, placebo-controlled and multicentre Phase-II-study to evaluate the antibacterial activity, safety and tolerability of bedaquiline. Only stage 2 of the study C208, which comprises the 24-week treatment period, is considered in the benefit assessment. The STREAM-study, a multicentre, randomised, open phase-III-study in a parallel group design, is included as a supplementary study. For stage 2 of the C208-study 161 people were screened and randomised 1:1 into the bedaquiline-arm (N=79) and the placebo/BR-arm (N=81). One person was randomised but did not receive the study medication due to AEs. By week 120 10 deaths occurred in the bedaquiline/BR-arm (12.7 %) and 3 in the placebo/BR-arm (3.7 %). There was no statistically significant difference between the treatment-arms. With regard to morbidity, which corresponds to the endpoint ‘cure’ in the study, there was a statistically significant difference in favour of bedaquiline/BR compared to placebo/BR with a high potential for bias due to the high proportion of missing values. No data was collected on health-related quality of life. At the end of the study, approximately 40% of the study participants in both study-arms had discontinued the study. There was no statistically significant difference in the occurrence of severe adverse events (AE), serious adverse events (SAE) and treatment discontinuations due to AEs between the treatment-arms. For AEs of any severity by system organ class and preferred term with an incidence ≥ 10%, a statistically significant difference was only found in favour of bedaquiline/BR for ‘tinnitus’. No significant differences were observed between the study-arms with regard to AEs of special interest (AESI).

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/976/#english

Year Published: 2024

URL for published report: https://www.g-ba.de/downloads/39-1464-6455/2024-02-01_AM-RL-XII_Bedaquiline_D-970_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/976/#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/