Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Gilteritinib (rezidivierte oder refraktäre akute myeloische Leukämie mit FLT3-Mutation)

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: Gilteritinib (XOSPATA) is indicated as monotherapy for the treatment of adult patients who have relapsed or refractory acute myeloid leukaemia (AML) with a FLT3 mutation. The benefit assessment is based on the pivotal study 2215-CL-0301 (ADMIRAL), a multicentre, open-label, randomised controlled, phase III, parallel-group (2:1) study evaluation the efficacy and safety of gliterinib compared to salvage chemotherapy in the treatment of patients with AML and FLT3 mutation who have relapsed or are refractory to first-line AML therapy. The study population included 247 and 124 patients in the gliterinib arm and salvage chemotherapy arm, respectively. Patients were stratified randomised by pre-selected savage chemotherapy (high-dose vs. low-dose) and response to first-line therapy. Primary endpoints were overall survival (OS) and the rate of patients with complete remission (CR) or CR with partial hematologic regeneration. Supportive evidence came from the multicentre, open-label, dose-escalating, phase I/II study 2215-CL-0101 (CHRYSALIS), which additionally included patients with more than one prior AML therapy. Gliterinib was shown to be superior to chemotherapy regarding OS in patients with FLT3 mutation and prior AML therapy. The observed effect is associated with an unclear risk of bias. Regarding morbidity, no conclusive results on patient-relevant outcomes could be made. There were no data available for the assessment of health-related quality of life. Regarding safety, there were statistically significant differences in favour of gliterinib compared to chemotherapy in the AE CTCAE grade ≥ 3 and treatment discontinuations due to AE. Additionally, there were statistically significant differences to the disadvantage of gliterinib regarding serious AE. Due to the short observation period in the control arm, early censoring and the open-label study design, there were significant uncertainties in the effects on safety.

Authors' recommendations: Gilteritinib (XOSPATA) is indicated as monotherapy for the treatment of adult patients who have relapsed or refractory acute myeloid leukaemia (AML) with a FLT3 mutation. The benefit assessment is based on the pivotal study 2215-CL-0301 (ADMIRAL), a multicentre, open-label, randomised controlled, phase III, parallel-group (2:1) study evaluation the efficacy and safety of gliterinib compared to salvage chemotherapy in the treatment of patients with AML and FLT3 mutation who have relapsed or are refractory to first-line AML therapy. The study population included 247 and 124 patients in the gliterinib arm and salvage chemotherapy arm, respectively. Patients were stratified randomised by pre-selected savage chemotherapy (high-dose vs. low-dose) and response to first-line therapy. Primary endpoints were overall survival (OS) and the rate of patients with complete remission (CR) or CR with partial hematologic regeneration. Supportive evidence came from the multicentre, open-label, dose-escalating, phase I/II study 2215-CL-0101 (CHRYSALIS), which additionally included patients with more than one prior AML therapy. Gliterinib was shown to be superior to chemotherapy regarding OS in patients with FLT3 mutation and prior AML therapy. The observed effect is associated with an unclear risk of bias. Regarding morbidity, no conclusive results on patient-relevant outcomes could be made. There were no data available for the assessment of health-related quality of life. Regarding safety, there were statistically significant differences in favour of gliterinib compared to chemotherapy in the AE CTCAE grade ≥ 3 and treatment discontinuations due to AE. Additionally, there were statistically significant differences to the disadvantage of gliterinib regarding serious AE. Due to the short observation period in the control arm, early censoring and the open-label study design, there were significant uncertainties in the effects on safety.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/509/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4287/2020-05-14_AM-RL-XII_Gilteritinib_D-503_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/509/#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/