Original Title: Arzneimittel-Richtlinie/Anlage XII: Avapritinib (Gastrointestinale Stromatumoren)

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: Ayvakyt is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation. The benefit assessment is based on the study NAVIGATOR (BLU-285-1101), a single-arm, multicentre, international phase I/II dose escalation study evaluating the safety, pharmacokinetics, pharmacodynamics and preclinical efficacy of Ayvakyt in patients with GIST and other relapsed/refractory solid tumors. The study consisted of two parts: Part I was a dose escalation phase (part I) assessing the maximum tolerated dose (MTD) and recommended dose for part II (RP2D). Part II was an expansion phase assessing the safety, tolerability and clinical efficacy of Ayvakyt with respect to the established starting dose (RP2D). The assessment included only that part of the study population covered by the indication (PDGRFa-D842V mutation) and treated according to the professional information. Therefore, 28 out of 237 patients (≥ 18 years) were considered. Primary endpoints included MTD, RP2D and a safety profile for Ayvakyt for phase I and overall response rate (ORR) as well as a safety profile for Ayvakyt for phase II. The indirect comparison presented with the dossier is not methodologically adequate and were not used to assess the benefit of Ayvakyt. Adequate comparative analyses on overall survival was not available. During median follow-up of 25 months, approximately one quarter of the patients died, yet a conclusive assessment of the effect of Ayvakyt on mortality was not possible. No patient relevant data were collected regarding morbidity and quality of life. All patients experienced AE during therapy phase with Ayvakyt. Almost all patients experienced severe AE and a vast majority experienced serious AE. Due to the uncontrolled study design and the limited sample size, the risk of bias potential is high and the reliability of the results is low.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/602/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4782/2021-04-15_AM-RL-XII_Avapritinib_D-583_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/602/#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/