Health-related quality of life following valoctocogene roxaparvovec gene therapy for severe hemophilia A in the phase 3 trial GENEr8-1.

Background: Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL).
Objectives: We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1.
Methods: Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 10 ¹³ vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes.
Results: For 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain.
Conclusion: Valoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA.
Competing Interests: Declaration of competing interests B.O.M. reports consulting fees from BioMarin Pharmaceutical Inc and Freeline. A.L.D. reports research funding from Sanofi, Takeda, Freeline, BioMarin Pharmaceutical Inc, and the American Thrombosis and Hemostasis Network; consulting fees from BioMarin Pharmaceutical Inc, Genentech/Roche, Kedrion, CSL Behring, and uniQure; and service on the board of the World Federation of Hemophilia USA. A.D.L. reports consulting or advisory panel fees from BioMarin Pharmaceutical Inc, Dova, CSL Behring, Merck, Catalyst, and HEME Biologics; and participation as a clinical trial investigator in trials sponsored by BioMarin Pharmaceutical Inc, Sangamo, and Pfizer. F.P. reports honoraria as a speaker for educational symposia by Grifols, Sanofi, and Takeda and as an advisory member for Sanofi and Roche. M.C.O. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; research grants from Pfizer, Roche, and Takeda; service as a clinical trial investigator for BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; speaker honoraria from Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Roche, and Takeda; travel support from Novo Nordisk, Roche, and Takeda; and participation in grant reviewing for Grifols. J.M. reports consulting fees from Baxalta, CSL Behring, Catalyst Biosciences, Freeline, LFB, Novo Nordisk, and Spark; research grants from and service as a clinical trial investigator for BioMarin Pharmaceutical Inc, CSL Behring, Novo Nordisk, Pfizer, Sobi, Roche, Novartis, Sanofi, and Unique; and speaker fees from Novo Nordisk, Pfizer, Sanofi, Sobi, Shire, Roche, Takeda, the International Society on Thrombosis and Haemostasis, and the World Federation of Hemophilia. K.P. reports consulting fees and research grants from Sobi, Octapharma, Novo Nordisk, and Pfizer; and served as a clinical trial investigator for uniQure, BioMarin Pharmaceutical Inc, and Roche. J-D.W. reports consulting fees from Bayer, Novo Nordisk, Pfizer, Chugai, Sanofi, Takeda, and Sobi; speaker fees from Bayer, CSL Behring, Novo Nordisk, Pfizer, Chugai, Sanofi, and Takeda; and service as a clinical trial investigator for Bayer, BioMarin Pharmaceutical Inc, Novo Nordisk, Pfizer, Roche/Chugai, and Sanofi. G.L. has received honoraria for participating in educational events from Novartis, LEO, Sobi, Alexion, Takeda, Novo Nordisk, and Sanofi; and consulting fees from UCB. A.G. reports honoraria for service on advisory boards from BioMarin Pharmaceutical Inc, Genentech, Pfizer, Bayer, ATHN, Novo Nordisk, uniQure, and Sanofi Genzyme; and travel grants from BioMarin Pharmaceutical Inc. E.C. reports consulting fees from Genentech, BioMarin Pharmaceutical Inc, Novo Nordisk, Takeda, Sanofi, HEMA Biologics, and CSL Behring; and speaker fees from Genentech. D.P. reports a travel grant from Pfizer. H.C. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Roche, and Sobi; served as a clinical trial investigator for BioMarin Pharmaceutical Inc, Bioverativ, CSL Behring, LFB, Octapharma, Roche, Pfizer, Sobi, and Takeda; reports speaker fees from BioMarin Pharmaceutical Inc, Pfizer, Roche, and Sobi; and reports travel grants from BioMarin Pharmaceutical Inc, CSL Behring, Octapharma, Roche, and Sobi. M.F.L.F. reports participation in advisory boards and receiving speaking fees from Shire/Takeda, Amgen, CSL Behring, Novo Nordisk, Bayer, LFB, Pfizer, and Sobi. E.M. reports consulting fees and travel support from BioMarin Pharmaceutical Inc and served as a clinical trial investigator for BioMarin Pharmaceutical Inc. M.W.S. reports consulting fees from Bayer, BioMarin Pharmaceutical Inc, Pfizer (DMC), Roche/Genentech, Sanofi, Spark (DMC), and Takeda; and research grants from BioMarin Pharmaceutical Inc, Freeline, Roche, Takeda, and uniQure. R.Klamroth reports consulting fees from Bayer, Biotest, BioMarin Pharmaceutical Inc, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; research grants from Bayer and LEO; speaker fees from Bayer, Biotest, BioMarin Pharmaceutical Inc, CSL Behring, Daiichi Sankyo, LEO, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; travel support from Bayer, Biotest, BioMarin Pharmaceutical Inc, CSL Behring, Daiichi Sankyo, LEO, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, and Sobi; and service as a clinical trial investigator for Bayer, BioMarin Pharmaceutical Inc, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche/Chugai, Sanofi, Takeda/Shire, Sobi, and uniQure. S.W.P. reports consulting fees from Apcintex, ASC Therapeutics, Bayer, BioMarin Pharmaceutical Inc, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Spark Therapeutics, Takeda, and uniQure; and service as a clinical trial investigator for BioMarin Pharmaceutical Inc, Freeline, Genentech/Roche, Sanofi, and uniQure. J.Q. is a former employee of BioMarin Pharmaceutical and may hold stock. H.Y., T.M.R., and W.Y.W. are employees and stockholders of BioMarin Pharmaceutical Inc. C.W.T., H.T., R.Kazmi, and T-L.K. have no competing interests to disclose.
(Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)