Original Title: Arzneimittel-Richtlinie/Anlage XII: Valoctocogen Roxaparvovec (schwere Hämophilie A)

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: Valoctocogene roxaparvovec (BMN 270) is approved for the treatment of severe haemophilia A in adults without a history of factor VIII inhibitors and without detectable antibodies to AAV5. The benefit assessment and an amendment are based on BMN 270-301, an ongoing open-label, single-arm phase III study. The study included 2 cohorts: a rollover population (n = 112) and a direct inclusion population (n = 22). The rollover population previously participated for ≤ 6 months in BMN 270-902, a non-interventional observational study, while the other patients were directly enrolled in BMN 270-301. One death was reported. Regarding 'All bleedings', 42 patients (31%) reported no bleedings. 79 (59%) patients reported no "Treated Bleedings". For the 'EQ-5D-5L-VAS' a statistically significant increase compared to baseline was reported. Results of the 'Haemophilia Activity List' (HAL) were included in the amendment. The total score of the HAL measures functional impairments which improve compared to baseline. Results of the QoL measure 'Haemo-QoL-A' show a statistically significant increase compared to baseline. There was no information on the assessment of clinical relevance for these PROs. Due to open study design, placebo effects cannot be ruled out. All patients experienced AE and 31 % experienced AE of CTCAE grade ≥ 3. SAEs were reported by 18 %. Elevated ALT levels were reported by 89 % and elevated AST levels by 35 %. Severe AEs were most commonly reported in the SOC 'investigations' (13 %). SAEs were present in 5 % of patients in the SOC 'infections and parasitic diseases'. Safety results for patients ≥ 60 years are limited. A before-after comparison and two indirect comparisons with external controls were not accepted for the benefit assessment due to various limitations. A comparative interpretation and evaluation of the results of BMN 270-301 to other therapeutic approaches is not possible due to the lack of an adequate control group. There is a high risk of bias and limited reliability of the results.

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/877/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-5902/2023-03-16_AM-RL-XII_Valoctocogen-Roxaparvovec_D-876_EN.pdf

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

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/877/#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/