Health-related quality of life in adults with hemophilia B after gene therapy with fidanacogene elaparvovec: results from the BENEGENE-2 trial
Makaleler > Tam Makale · 2025
Yazarlar: Kaan Kavakli, Adam Cuker, Laurent Frenzel, Jiaan-Der Wang, Catherine N. Bagot, Fahri ŞAHİN, Huyen Tran, Hazzaa Alzahrani, Davide Matino, Jeremy Rupon, John McKay, Lisa J. Wilcox, Francesca Biondo, Delphine Agathon, Sheena Thakkar, Pengling Sun, Frank Plonski, Sylvia von Mackensen
Journal of Thrombosis and Haemostasis, Uluslararası, Wos, 2025, cilt 24, ss 132-145
DOI: 10.1016/j.jtha.2025.09.029
Özet
BACKGROUND: BENEGENE-2 is an ongoing phase 3 trial of fidanacogene elaparvovec, an adeno-associated virus gene therapy vector delivering a high-activity factor (F)IX variant, FIX-R338L (FIX-Padua). OBJECTIVES: To assess patient-reported outcome measures in BENEGENE-2. METHODS: Eligible males (N = 45) with hemophilia B received a single fidanacogene elaparvovec infusion after ≥6 months of FIX prophylaxis. Participants completed assessments pre- and post-gene therapy, including the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), Hemophilia Activities List (HAL), Patient Global Impression of Change-Hemophilia, Hemophilia Life Impacts Questionnaire, and European Quality of Life 5-Dimensions 5-levels. RESULTS: Post-gene therapy, more participants (64.4% vs 28.9%) were free from bleeds compared with pre-gene therapy. Overall, 64.4% of participants did not require exogenous FIX infusions post-gene therapy. Changes from pre- to week 52 post-gene therapy suggested improved health-related quality of life in the key secondary endpoints of the Haem-A-QoL Physical Health domain (mean [SD] score change, -7.7 [15.8]; P = .005) and the HAL Complex Lower Extremity Activities score (mean [SD] score change, 7.6 [19.6]; P = .024). Additionally, there was a mean (SD) improvement of -11.2 (9.1), P < .001, in the Haem-A-QoL total score, and 6.7 (10.9), P < .001, in the HAL total score. In the exploratory endpoints, changes in the European Quality of Life 5-Dimensions 5-levels index score (mean [SD] score change, 0.05 [0.10]; P = .003) and visual analog scale (mean [SD] score change, 5.8 [15.6]; P = .030) suggested improved health status. Overall, 56.1% of participants reported that their overall impression of life with hemophilia (Patient Global Impression of Change-Hemophilia) had "greatly improved." Improvements were observed in Hemophilia Life Impacts Questionnaire domains related to living with and treating hemophilia. CONCLUSION: Fidanacogene elaparvovec improved health-related quality of life and health and functional status in adults with hemophilia B.