Original Title: Arzneimittel-Richtlinie/Anlage XII: Etranacogen Dezaparvovec (Hämophilie B)

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: Etranacogen Dezaparvovec (EtranaDez, Hemgenix®) is approved for the treatment of severe and moderate hemophilia B (congenital FIX-deficiency) in adults without a history of FIX-inhibitors. The benefit assessment is based on the pivotal study HOPE-B (CT-AMT-061-02), an open-label, single-arm, multicenter, multinational phase-III-study in men with moderate to severe haemophilia B. A total of 67 patients were subsequently included in the lead-in period and 54 were finally treated with EtranaDez. The primary endpoint was defined as the annualized bleeding rate (ABR). Other endpoints included health status, pain, functional impairment and quality of life, as well as FIX-activity and FIX-replacement-therapy. One death occurred during the 2-year follow-up period after the EtranaDez treatment. With regard to morbidity, data on bleeding events, FIX-activity, FIX-replacement-therapy and health status were presented but were considered as not-patient-relevant and were therefore not considered for the benefit assessment. During the 2-year-follow-up period for total bleedings events an ABR of 1,0 [95% KI: 0,67; 1,52] and for treated bleedings an ABR of 0,82 [95%-CI 0,46; 1,48] was observed. Bleedings occurred in 23 of 54 patients 22 days – 24 months post-treatment. For the EQ-5D-VAS, BPI-SF and HAL measurement instruments and Quality of life, assessed using the Hem-A-QoL measurement only minor changes were observed on average compared to the baseline value. Up to the 2-year data cut-off, severe AE occurred in 20% of the 54 patients and serious AE in 26%. In 1 patient, an AE led to early discontinuation of the EtranaDez infusion, so that only a partial dose was administered. Common AE of any severity concerned the system-organ-classes infections and infestations (incidence 74%), musculoskeletal and connective tissue disorders (67%), general disorders and administration site conditions (56%). AE of special interest were e.g., unexpected reactions (4 %), AE related to the application procedure (11 %), any (re)occurrence of cancer (6 %, serious 2 %, severe 2 %), AE related to concomitant medication (4 %) and AE related to product failure (2 %). In overall, due to the single-arm study results, no conclusions can be drawn regarding the effects of EtranaDez on mortality, morbidity, QoL and safety.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/953/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-6233/2023-10-19_AM-RL_XII_Etranacogen%20Dezaparvovec_D-937_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/953/#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/