Original Title: Arzneimittel-Richtlinie/Anlage XII: Tagraxofusp (Blastische plasmazytoide dendritische Zellneoplasie, Erstlinie)

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: Tagraxofusp (TX) is approved for first-line (FL) treatment of adults with blastic plasmacytoid dendritic cell neoplasia (BPDCN). The benefit assessment of TX is based on the pivotal study STML-401-0114, which is a multicentre, open-label, single-arm phase I/II trial for the treatment of adults with FL or relapsed/refractory (R/R) BPDCN and adults with acute myeloid leukaemia (high-risk or R/R) with TX. The study was divided into four stages. Only the FL BPDCN patients receiving the approved liquid formulation and dose of 12 μg/kg/day of TX are considered in this benefit assessment, so that only results of a subpopulation of the stages 1-3 (N=29) are assessed. 62.1% of patients died between the first dose and the final data cut-off. Clear information on the reasons for censoring 11 patients is not available for the benefit assessment and it does not seem certain that all patients who were still alive were followed up until the final data cut-off. The median overall survival was 25.8 months [95% CI: 9.7; 53.9]. The effect of TX on mortality cannot be assessed due to the lack of a control group. A potential influence of any follow-up therapies cannot be conclusively assessed. For the endpoint category morbidity, no results on patient-relevant endpoints are available. Results on the endpoints complete remission and rate of stem cell transplant are not directly used for the benefit assessment. Data on quality of life were not collected. All patients experienced adverse events (AE) during treatment with TX. 87.1% experienced severe AE and 40.6% serious AE (SAE). For 15.6% the SAE “vascular disease” was reported. The AE of special interest "drug-related hepatic disorders " occurred in almost 80 % of the patients. Due to the lack of a control group, no comparative evaluation regarding the occurrence of safety events is possible. In total, the potential for bias was assessed as high on the basis of the single-arm study design and the reliability of the information is limited.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/707/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-5157/2021-12-02_AM-RL-XII_Tagraxofusp_D-667_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/707/#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/