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 × 10¹³ 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.