Original Title: Arzneimittel-Richtlinie/Anlage XII: Blinatumomab (Neues Anwendungsgebiet: Akute lymphatische B-Zell-Leukämie, Hochrisiko-Erstrezidiv, Ph-, CD19+, ≥1 und <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: Blinatumomab is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor ALL as part of the consolidation therapy. For the benefit assessment, the pharmaceutical company submitted data from the pivotal 20120215 marketing authorisation study. The 20120215 study is an ongoing, international, multicentre, randomised, controlled, open-label phase III study to investigate the efficacy, safety and tolerability of blinatumomab as consolidation therapy versus high-risk consolidation chemotherapy (HC) in paediatric patients with high-risk first relapse of Ph-, CD19+ B-precursor ALL. The study was conducted in 47 study sites across 13 countries. Patients under 18 years of age in the first relapse after induction therapy and two cycles of HC were enrolled. The total of 108 patients enrolled were stratified according to age and bone marrow/ MRD status and randomised in a 1:1 ratio to the two study arms. They received either one cycle of blinatumomab (one treatment cycle over 4 weeks as a continuous infusion; N = 54) or HC3 (administration of the chemotherapy regimen 2 over one week as an infusion and three weeks treatment-free period; N = 54) as further consolidation therapy. Patients will be observed as part of a safety follow-up after the last dose with the study medication within seven days prior to allo-HSCT. In addition, they undergo a short-term efficacy follow-up of 12 months and a long-term follow-up of up to 36 months after allo-HSCT. For the endpoint of overall survival, there is a statistically significant difference in favour of blinatumomab compared to HC3 to an extent that is assessed as a very significant improvement. The result for the EFS endpoint shows a statistically significant benefit of blinatumomab compared to HC3. No data were collected on the health-related quality of life. In the overall assessment of the endpoints of side effects, there is a statistically significant advantage of blinatumomab with regard to the severe AEs (CTCAE grade ≥ 3) and with regard to the SAEs". In the category of side effects, a significant advantage of blinatumomab over HC3 was found in the overall assessment. In the overall assessment, the G-BA comes to the conclusion that a considerable additional benefit of blinatumomab over HC3 is established for paediatric patients aged 1 year or older with high-risk first relapse of Philadelphia chromosome negative, CD19 positive B-precursor ALL as part of consolidation therapy especially due to the extent of the prolongation of survival and in view of the available results on event-free survival and side effects, which support the overall additional benefit.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/720/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5233/2022-01-20_AM-RL-XII_Blinatumomab_D-703_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/720/#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/