Original Title: Arzneimittel-Richtlinie/Anlage XII: Fedratinib (Myelofibrose)

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: Fedratinib is indicated for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are Janus Associated Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. For the benefit assessment, the pharmaceutical company presented results of the multicentre, globally conducted, randomised, double-blind, three-arm phase III study JAKARTA. Patients were randomised 1:1:1 to the three treatment arms, fedratinib 400 mg/day (N = 96 patients), fedratinib 500 mg a day (N = 97 patients), and placebo (N = 95). The 500 mg/day treatment arm is not relevant for the benefit assessment since the dosage is non-conformant with the product information. Patients should be treated according to the protocol in all treatment arms for at least six treatment cycles of 28 days each. Results of the data cut-off from 01.05.2013 were presented in the dossier by the pharmaceutical company. On this day, all study participants were unblinded. At this time, the median duration of observation was 62 weeks in the 400 mg/day fedratinib arm and 24.0 weeks in the placebo arm. Mortality, morbidity, and adverse event results are available from the JAKARTA study for the benefit assessment of fedratinib for treating disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis who are Janus Associated Kinase (JAK) inhibitor naïve. The study was discontinued prematurely due to the occurrence of Wernicke's encephalopathy. Overall, the results on overall survival are of small significance. Statistically there is no difference. A statistically significant advantage can be observed for the endpoints spleen response and symptom burden assessed by modified MFSAF. The advantage in spleen response combined with an advantage in symptom response is considered a significant, clinically relevant improvement. Treatment with fedratinib resulted in a statistically significant higher incidence of serious side effects events than placebo.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/662/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-5003/2021-09-02_AM-RL-XII_Fedratinib_D-650_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/662/#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/