Original Title: Arzneimittel-​​​Richtlinie/Anlage XII: Tisagenlecleucel (Neubewertung nach Fristablauf: Akute lymphatische B-Zell-Leukämie)

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: Tisagenlecleucel, Kymriah is indicated for the treatment of paediatric and young adult patients up to and including 25 years of age with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse. The benefit assessment is based on the pivotal phase II studies ELIANA (CCTL019B2202) and ENSIGN (CCTL019B2205J). Both studies evaluated the efficacy and safety of Kymriah in children, adolescents and young adults with relapsed/refractory (r/r) B-cell ALL (and lymphoblastic lymphoma in ENSIGN) and lasted 5 years from infusion. Study populations included 97 and 64 patients receiving infusion with Kymriah in ELIANA and ENSIGN, respectively. Primary endpoints were complete/partial response (CR/CRi) within the first 3 months after infusion with Kymriah (ELIANA) and overall response rate (ORR) within first 6 months after infusion (ENSIGN). Special attention is given to the analysis population. All patients included in the studies are relevant for the benefit assessment, not only those treated with Kymriah. Several external control studies were submitted with the dossier. The results of the indirect comparisons using external control studies are potentially biased and were therefore not used for the benefit assessment. Of the patients enrolled, 45.6% and 48.9% died in ELIANA and ENSIGN, respectively. ELIANA did not achieve median survival yet with a median observation time of 24.9 months. ENSIGN had a median survival of 25.9 with median observation time of 13.6 months, yet mortality cannot be assessed conclusively based on present data. AE in general, and especially AE cytokine release syndrome, occurred in a large proportion of patients, mainly during the first 8 weeks after infusion. In view of the lack of a valid comparison, the limited sample size and the selective survey after 12 months at the latest after infusion, a conclusive safety evaluation including long-term safety was not possible.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/533/#english

Year Published: 2020

URL for published report: https://www.g-ba.de/downloads/39-1464-4457/2020-09-17_AM-RL-XII_Tisagenlecleucel_D-529_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/533/#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/