Original Title: Arzneimittel-Richtlinie/Anlage XII: Blinatumomab (Neues Anwendungsgebiet: Akute lymphatische B-Zell-Leukämie, rezidiviert oder refraktär, Ph+ CD19+)

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: The benefit assessment of blinatumomab (Blincyto) as monotherapy relates to the indication of the treatment of adults with Philadelphia chromosome positive (Ph+) CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL). Patients with Philadelphia chromosome positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors and have no alternative treatment options. The benefit assessment is based on the pivotal study 20120216 (ALCANTARA), a single-arm, open-label, multicentre, phase II study evaluating the efficacy and safety of blinatumomab in adults with relapsed/refractory Ph+ B-precursor acute ALL. The study consists of a 3-week screening period, an induction treatment (2 cycles, each 6 weeks), a consolidation treatment, a safety follow-up and a long-term follow up. Outcomes include overall survival, MRD remission, rate and duration of CR or CRh, rate of alloHSCT, and AEs. Patient-reported outcomes were not collected. Due to a lack of control, the results observed in the ALCANTARA trial do not allow valid conclusions regarding the effect of blinatumomab on overall survival. The estimated median survival with blinatumomab was 9.0 months [95% CI 5.7; 13.5] and the probability of survival at 12 months was reported to be 42% [95% CI 28%; 56%]. For morbidity, no results on patient-relevant endpoints were available. No data on quality of life was available. Due to the uncontrolled data, no conclusions on safety can be derived in comparison to other antileukemic therapies. The pharmaceutical company additionally presented propensity score-based analyses based on the ALCANTARA study and a retrospective cohort study (study 20160462) for an indirect comparison of blinatumomab with a salvage therapy. For the benefit assessment, the indirect comparison is not to be found valid due to considerable methodological limitations and uncertainties.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/642/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4925/2021-07-15_AM-RL-XII_Blinatumomab_D-610_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/642/#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/