Original Title: Arzneimittel-Richtlinie/Anlage XII: Glasdegib (akute myeloische Leukämie (AML), Kombination mit Cytarabin (LDAC))

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: Glasdegib is approved for the indication of newly diagnosed de novo or secondary acute myeloid leukaemia (AML) in adults who are not eligible for standard induction chemotherapy. The pivotal study B1371003 is a multinational, multicentre, partially randomised, open-label phase Ib/II study. Only the randomised part of phase II is relevant for the benefit assessment, in which patients with AML did not receive standard induction chemotherapy. The random assignment to the two groups Glasdegib+LDAC vs. low dose Cytarabine (LDAC) was done in a 2:1 ratio. Benefit: For overall survival, there was a statistically significant benefit in favour of Glasdegib+LDAC compared to the LDAC control group. The statistically significant benefit in overall survival in favour of glasdegib+LDAC was also shown in the sensitivity analyses. Some uncertainties exist regarding randomisation, due to the small number of cases in the study (N = 78 versus N =38) and the imbalances of prognostic factors. Due to the robust results, these uncertainties are considered of low risk of bias. Quality of life data was not collected in study B1371003, phase II. Safety Assessing the adverse events, the high risk of bias due to the unblinded study design must be taken into account. In addition, the number of patients included in the safety population is low, with N = 75 (Glasdegib+LDAC) and N = 36 (LDAC). Both of these factors it is difficult to interpret the safety results. In the time-to-event analyses, there were no statistically significant differences between Glasdegib+LDAC and LDAC in the overall rates of serious and severe AEs, respectively.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/579/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4705/2021-12-18_AM-RL-XII_Glasdegib_D-565_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/579/#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/