Original Title: Arzneimittel-Richtlinie/Anlage XII: Ripretinib (Gastrointestinale Stromatumoren (GIST), ≥ 3 Vortherapien)

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: Ripretinib (QINLOCK®) is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumour (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib. The benefit assessment is based on the randomised, double-blind, placebo-controlled phase III INVICTUS study. In the study, 129 patients were randomised in a 2:1 ratio to the two treatment arms (test arm: N = 85, control arm: N = 44). Treatment in both arms was carried out in a double-blind phase until disease progression according to mRECIST criteria (modified Response Evaluation Criteria in Solid Tumours Version 1.1; GIST-specific), after which the patients were transferred to an open-label phase. For the endpoint of overall survival, there was a statistically significant difference to the advantage of ripretinib versus placebo, with a high potential of bias. For the morbidity, the endpoint general health status (EQ-5D-5L-VAS) showed a statistically significant benefit of ripretinib compared to placebo with a high potential for bias. In addition, there was no statistically significant difference between treatment arms for the disease symptomatology domains of the EORTC QLQ-C30 at high potential for bias. Significant for the high potential of bias are the uncertainties in the follow-up of the EQ-5D-5L-VAS and EORTC QLQ-C30 and the differences in response rates between the treatment arms. The endpoint health-related quality of life (EORTC QLQ-C30) showed a statistically significant benefit of ripretinib compared with placebo only in the domains physical function and role function with high potential for bias. The same uncertainties exist as in the disease symptomatology of the EORTC QLQ-C30. Almost all study participants experienced at least one adverse event (AE). There was a statistically significant effect in favor of ripretinib in the overall rate of severe AE and serious AE. However, the results on side effects also include events due to progression and symptomatology of the underlying disease, so these should be considered as being prone to a high potential of bias.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/778/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5469/2022-06-16_AM-RL-XII_Ripretinib_D-782_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/778/#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/