Original Title: Arzneimittel-Richtlinie/Anlage XII: Ivosidenib (Akute Myeloische Leukämie mit IDH1-R132-Mutation, Erstlinie, Kombination mit Azacitidin)

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: Ivosidenib in combination with azacitidine is approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1)-R132 mutation who are not eligable to recieve intensive induction chemotherapy. Benefit assessment is based on the pivotal study AGILE, which included adult patients with untreated AML with an IDH1-R132 mutation who were not suitable for intensive chemotherapy. Ivosidenib in combination with azacitidine was compared to placebo in combination with azacitidine. Mortality Median survival time is significantly longer in the ivosidenib arm than in the placebo arm. Morbidity Time-to-event analyses for symptom scales and items of the EORTC QLQ-C30 showed an advantage for ivosidenib in the domain constipation; for the other domains there was no statistically significant difference between treatment groups. There was also no statistically significant difference in health status measured with the EQ-5D VAS between ivosidenib and placebo. No statistically significant difference in transfusion independence was observed in participants who were followed-up for at least 24 weeks. Quality of life Time-to-event analyses of the EORTC QLQ-C30 functional scales and global health status/quality of life showed a statistically significant difference in favor of ivosidenib in emotional functioning. However, this advantage is not observed in any other scale of the EORTC QLQ-C30. Adverse events There was no statistically significant difference in the time to occurrence of serious AEs, SAEs and AEs leading to treatment discontinuations between ivosidenib and placebo. There were statistically significant differences in individual SOC and PT.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/973/#english

Year Published: 2024

URL for published report: https://www.g-ba.de/downloads/39-1464-6410/2024-01-18_AM-RL-XII_Ivosidenib_D-954_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/973/#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/