Original Title: Arzneimittel-Richtlinie/Anlage XII: Selumetinib (Neubewertung nach Fristablauf: Neurofibromatose (≥ 3 bis < 18 Jahre, Typ 1))

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: Selumetinib is approved for the treatment of symptomatic, unresectable plexiform neurofibromas (PN) in neurofibromatosis type 1 (NF1) in children ≥3 years. The benefit assessment is based on the pivotal study SPRINT, an open-label, single-arm, multicenter study in 2 phases on the safety and efficacy of selumetinib in children and adolescents with symptomatic, inoperable PN due to NF1 (N=50). Phase II stratum 1 of the SPRINT study is relevant for the benefit assessment (PN-related morbidity was already present at the time of study inclusion), as this describes the present indication. Data were available for the data-cut off 31st March 2021 for a median treatment period of 4.6 years. No deaths were reported during the observation period. No statistical difference in PROMIS scales “mobility”, upper extremity” before starting treatment cycle 13 to baseline were observed in patients aged 8-18 years. For patients aged 5-7 years only descriptive data were available. Descriptive data was also available for the following endpoints: Improvements were observed over time compared to baseline for worst pain and self-reported global assessment of clinical change for tumor-associated morbidity. Improvements, but also worsening in symptoms, evaluated by a symptom checklist, was observed before cycle 25. Furthermore, an improvement of 21-38%, but also worsening in 12-20 of patients in general health-related quality of life measured by PedsQL global score was observed for the study population. However, bias in favor of selumetinib is possible due to nonresponse of the school function subscale. Adverse events (AE) occurred in 98%, severe AE in 68% and serious AE in 30% of all patients. AE, leading to termination of study medication was observed in 12 % of the study population. The effect of Selumetinib on mortality, morbidity, quality of life and safety cannot be conclusively evaluated on the basis of the single-arm trial submitted for assessment.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/964/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6346/2023-12-21_AM-RL-XII_Selumetinib_D-959_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/964/#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/