Original Title: Arzneimittel-Richtlinie/Anlage XII: Avapritinib (Neues Anwendungsgebiet: systemische Mastozytose, 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: Avapritinib is approved for the treatment of adults with advanced systemic mastocytosis (AdvSM) after at least one systemic therapy. The benefit assessment of avapritinib is based on the pivotal study PATHFINDER and the study EXPLORER. PATHFINDER is an ongoing multicentre, open-label, uncontrolled phase II study investigating the efficacy and safety of avapritinib in adults with AdvSM. EXPLORER is an ongoing multicentre, open-label, uncontrolled phase I study with a phase II expansion to investigate the safety, tolerability, PK/PD and antineoplastic activity of avapritinib in adults with AdvSM or other R/R myeloid diseases. Two indirect comparisons were not accepted for the benefit assessment because sufficient comparability of populations was not demonstrated or too limited information was available for the assessment. In PATHFINDER, 16% of patients died at a median follow-up (FU) time of 12 months, and in EXPLORER, 25% of patients died at a median FU time of 22 months. At data cut-off , the median survival time has not yet been reached in either study. For the Patient Global Impression of Symptom Severity (morbidity) and the EORTC QLQ-C30 (morbidity and quality of life) only descriptive results are available. Due to a lack of patient relevance, the endpoint complete remission is only presented as a supplement in the benefit assessment. The median treatment duration is 9 months (PATHFINDER) and 21 months (EXPLORER). AE occurred in all patients. AEs of CTCAE grade ≥ 3 were documented in 72% and 75% of patients, respectively. SAEs were reported in 40% (PATHFINDER) and 42% (EXPLORER) of patients. 18% of patients discontinued therapy due to AEs in PATHFINDER and no one in EXPLORER. A comparative interpretation and evaluation of the endpoints to other therapeutic approaches is not possible due to missing control groups. The potential for bias was assessed as high on the basis of the single-arm study design of both studies and the confidence in the results is limited.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/817/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5616/2022-09-15_AM-RL-XII_Avapritinib_D-798_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/817/#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/