Original Title: Arzneimittel-Richtlinie/Anlage XII: Epcoritamab (Diffus großzelliges B-Zell-Lymphom, nach ≥ 2 Vortherapien)

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: Epcoritamab as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. It is is approved as a medicinal product for the treatment of rare diseases under Regulation (EC) No. 141/2000 of the European Parliament and the Council of 16 December 1999. The benefit Assessment is based on the pivotal, single-arm phase I/II GCT3013-01 study. Relevant for the present benefit assessment is the cohort of patients with r/r DLBCL in the expansion phase of the study. Patients with r/r DLBCL had to have CD20-positive disease and prior therapy with at least two lines of systemic antineoplastic therapy, including at least one anti-CD20 antibody-containing therapy. Patients who were eligible for curative intensive salvage therapy followed by high-dose chemotherapy with haematological stem cell transplantation (HSCT) were not enrolled. Of 219 patients screened, 157 suitable patients were enrolled in the study, 139 of whom were diagnosed with DLBCL. This population forms both the full analysis set (FAS) and the safety population. The study has been conducted at a total of 54 study sites in Australia, North America, Europe and Asia. The primary endpoint of the was the overall response rate (ORR), secondary endpoints included the overall survival (OS) and endpoints of the categories of morbidity, health-related quality of life and side effects. From four data available data cut-offs the data cut-off from 21.04.2023 (longest duration of observation) was used for the benefit assessment. For 86 (61,9) patients, overall (complete or partial) response was observed however, at time of the data cut-off 77 (55.4%) patients of the FAS had died. Due to a very high drop-out rate, data on quality of life could not be analysed. An adverse event (AE) occurred in almost all patients (99.3%). Serious adverse events (SAE) occurred in 68.3%, severe adverse events (CTCAE grade ≥ 3) in 69.1% and 15,8% discontinued the study therapy due to adverse events. Immune system disorders (28.8%) and infections and infestations (29.5 %) occurred as serious adverse events with an incidence ≥ 10% of patients by system organ class (SOC). An adverse event of special interest was cytokine release syndrome (CRS), which occurred as an adverse event, regardless of severity, in 49.6% of patients and as a serious adverse event in 28.8% of patients.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/1004/#english

Year Published: 2024

URL for published report: https://www.g-ba.de/downloads/40-1465-10368/2024-04-04_AM-RL-XII_Epcoritamab_D-980_TrG_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/1004/#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/