Original Title: Arzneimittel-Richtlinie/Anlage XII: Autologe anti-CD19-transduzierte CD3-positive zellen (mantelzell-lymphom, vorbehandelte atienten)

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: Autologous anti-CD19-transduced CD3+ cells (Brexucabtagene autoleucel; Tecartus)); Tecartus is approved for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor. Benefit assessment is based on the pivotal study ZUMA-2, an uncontrolled, multicentre phase II study to determine the safety and efficacy of Tecartus in adults with r/r MCL. The indirect comparison submitted with the dossier on the basis of a matching-adjusted indirect comparison (MAIC) was assessed as inadequate for the benefit assessment due to the lack of comparability with the ZUMA-2 study and was not used. At month 24, the Kaplan-Meier estimate for overall survival was 66.5% (95% CI: [52.8; 77.1]). An interpretation and assessment of the estimated survival time was not possible due to absence of a control group. The EQ-5D-VAS showed a significant decrease 4 weeks after the infusion (mean: -7.8 points, 95% CI: [-12.8; -2.7]), which decreased until month 3 (mean: -2.4 points, (95% CI: [-7.0; 2.3]). An interpretation and assessment of changes in the EQ-5D-VAS was not possible due to absence of a control group. No data on quality of life were collected within the ZUMA-2 study. The safety of therapy with Tecartus could not be conclusively assessed due to absence of a control group, incomplete reports of AEs before Tecartus infusion and the partially selective collection of AEs after Tecartus infusion. Severe AEs (99 %) and SUEs (71 %) occurred frequently after infusion with Tecartus. In an amendment, an indirect comparison based on individual patient data of the SCHOLAR-2 study was assessed. The SCHOLAR-2 study is a retrospective, multicentre observational study based on patient records of patients with r/r MCL. This comparison was also assessed as inadequate due to lack of comparability of the study population with ZUMA-2 as well missing adjustment for important prognostic factors.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/657/#english

Year Published: 2021

URL for published report: https://www.g-ba.de/downloads/39-1464-4964/2021-08-05_AM-RL-XII_Autologe-Anti-CD19-transduzierte-CD3-positive-Zellen_D-633_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/657/#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