Original Title: Arzneimittel-Richtlinie/Anlage XII: Ivosidenib (Cholangiokarzinom mit IDH1-R132-Mutation, nach mind. 1 Vortherapie)

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 monotherapy is approved for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy. The benefit assessment is based upon the pivotal, randomised, double-blind, placebo-controlled phase III ClarIDHy study. In this study, Ivosidenib was compared with placebo; additional supportive measures as part of best supportive care (BSC) were permitted in both study arms. Benefit: No statistically significant difference was detected between the treatment arms with respect to overall survival. Progression-free survival (PFS) was significantly longer with Ivosidenib + BSC compared to placebo + BSC. Since the response rates for all patient-reported outcome measures (PROMs) were low (<70%), it was not possible to determine if the PFS-advantage has a meaningful impact on patient’s morbidity and quality of life (QoL). A significant interaction revealed a potential survival benefit for patients with an initial ECOG-Performance status of 0 (indicating higher functioning) compared to patients with an ECOG status of ≥1. Because such an interaction was not found for the safety endpoints, and other endpoints were not evaluated, the certainty of evidence for this subgroup finding is low. In addition, there was a high risk of bias for the survival analysis, since 43 (70.5%) of patients had switched from the Placebo arm to the Ivosidenib arm after disease progression. QoL: Because of low response (<70%), it was not possible to evaluate a possible effect of Ivosidenib on QoL. Safety: Adverse events (AE) occurred in almost all patients in both study arms. Time to serious AEs, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs as well as AEs of special interest did not differ between study arms. The risk of bias is high due to informative censoring (patients in the Placebo arm were censored at the time of treatment-switch).

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/972/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6411/2024-01-18_AM-RL-XII_Ivosidenib_D-955_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/972/#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/