Original Title: Arzneimittel-​​​​Richtlinie/Anlage XII: Blinatumomab (neues Anwendungsgebiet: akute lymphatische Leukämie, pädiatrische Patienten im Alter von 1 Jahr oder älter)

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: BLINCYTO is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome-negative, CD19-positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation. The benefit assessment is based on the pivotal study MT103-205, an uncontrolled, multicentre phase I/II study evaluating the efficacy, safety, and tolerability of blincyto in paediatric and adolescent patients with relapsed/refractory B-precursor ALL. The study is divided into two phases: Phase I is designed to investigate different doses of blincyto, one of which was evaluated for efficacy and safety in the subsequent Phase II. Phase II corresponded to a two-stage design, in which efficacy had to be demonstrated in at least 2 of 21 patients in the first stage, before 19 further patients could be included. The core study consisted of screening, treatment and a follow-up phase of 30 days after the last administered dose of blinatumomab or before the start of subsequent non-protocol therapy. Primary endpoint of phase I was the maximum tolerated dose (MTD) and of phase II complete remission during induction therapy (2 cycles of blincyto lasting 6 weeks each). The external control studies submitted with the dossier were not considered in the benefit assessment due to bias. Efficacy assessment showed that 68.6% patients died by the end of the study with a median survival time of 7.5 months [95% CI: 4.0 to 11.8], yet no clear conclusions can be drawn based on a lack of valid comparison. All patients experienced as least one AE during therapy with blincyto and more than half of the study population experienced an AE of CTCAE grade 3 or higher or a serious AE. Given the lack of valid comparison, the limited sample size and the short observation period, a conclusive safety assessment is not possible.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/468/#english

Year Published: 2018

URL for published report: https://www.g-ba.de/downloads/39-1464-3920/2019-08-15_AM-RL-XII_Blinatumomab_D-397_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/468/#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/