Original Title: Arzneimittel-Richtlinie/Anlage XII: Brexucabtagen-Autoleucel (Neues Anwendungsgebiet: rezidivierte oder refraktäre B-Zell-Vorläufer akute lymphatische Leukämie, ab 26 Jahren)

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: Brexucabtagen autoleucel (brexu-cel), a novel CD19-directed chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). The benefit assessment is based on the pivotal ZUMA-3 study, a one-arm, open-label and multicentric phase-Ib/II-study. The objective of the first portion of the study was to confirm the estimated dose. The aim of the second portion was to assess the objective response rate. The bias potential is considered as high due to the missing control group. An indirect comparison was rejected because of methodological shortcomings and limited comparability of study populations between clinical and historical control group. Therefore it is not possible to draw conclusions on mortality and morbidity endpoints due to the missing control group. Of 81 patients in the full analysis set, 41 (50,6%) deceased at the time of the relevant data cut off date. 35 were still under observation. Median overall survival was 23.1 months (95%-KI: [13,5; n.o.]) and the median observation time was 25.1 months. Side effects were mainly collected between the day of infusion and three months after infusion. Six patients died after an adverse event. Nearly every UE of special interest occurred in the trial, especially the cytokine release syndrom. The safety assessment is limited due to differences in reporting between treatment phases and the missing control group. After the treatment with brexu-cel 11 patients received an allogeneic stemcell transplantation which has a curative intention.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/878/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-5907/2023-03-16_AM-RL-XII_Brexucabtagen-Autoleucel_D-875_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/878/#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/