Original Title: Arzneimittel-Richtlinie/Anlage XII: Tebentafusp (Uveales Melanom, HLA-A*02:01-positiv)

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: Tebentafusp is approved as a monotherapy in the treatment of HLA (human leukocyte antigen)-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. The benefit assessment of tebentafusp is based on the pivotal studies IMCgp100-202 (202) and IMCgp100-102 (102). 202 is a randomized, multicenter, controlled phase II study investigating the safety and efficacy of tebentafusp vs. dacarbazine, ipilimumab, or pembrolizumab in HLA-A*02:01 positive adult patients with untreated advanced or metastatic uveal melanoma detected by genetic testing. Survival was the primary endpoint of Study 202, showing a significant benefit for tebentafusp. The potential for bias in Study 202 for the overall survival endpoint is considered low. A subgroup analysis of the overall survival endpoint showed a significant interaction between treatment and the stratification characteristic LDH (p = 0.04). However, the effects were equidirectional, with the group with LDH ≤ ULN benefiting more from therapy with tebentafusp and showing significantly longer overall survival in both arms. In contrast, there was no statistically significant difference for the subgroup with LDH > ULN. It should be noted that median survival in the group with an LDH > ULN was significantly shortened in both treatment groups, and the effect estimate suggests an effect of the same direction. Conclusions on effects in this subgroup for other patient-relevant outcomes cannot be made because no subgroup analyses of safety could be identified in the submitted documents and no usable data were available for the other patient-relevant outcomes. In study 102, 69 of the 126 study participants had died at the data cut timepoint. The company does not provide information on the reasons for the censoring of the remaining study participants. Due to the lack of a control group, the effect of tebentafusp on overall survival in pretreated patients with uveal metastatic melanoma cannot be conclusively assessed. The effect of tebentafusp on morbidity cannot be assessed from the data presented. The impact of tebentafusp on quality of life cannot be assessed based on the data presented. An assessment of the safety of tebentafusp is not possible due to the lack of adequate effect estimate within study 202 and the lack of a control group within study 102.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/822/#english

Year Published: 2022

URL for published report: https://www.g-ba.de/downloads/39-1464-5660/2022-10-20_AM-RL-XII_Tebentafusp_D-768_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/822/#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/