Impact of valoctocogene roxaparvovec on hemophilia-free mind: A visual multidimensional method

Introduction Thehemophilia-free mind (HFM) has been proposed as an aspirational aim for hemophilia treatments. HFM is conceptualized as minimization of physical and psychological burden, leading to a reduction of preoccupation of patients with their disease. The aim of this study was to develop a method to quantify HFM and to describe changes in HFM among people with hemophilia A receiving valoctocogene roxaparvovec gene therapy. Method Clinical and methodological experts convened to align on conceptualization and measurement of HFM. Dimensions of HFM were mapped to existing clinical outcomes and patient-reported outcome (PRO) questionnaires from the GENEr8-1 trial of valoctocogene roxaparvovec in severe hemophilia A. Clinical relevance of the mapped measures and thresholds representing achievement of HFM were agreed. Proportions of participants achieving thresholds at baseline and Week 104 in GENEr8-1 quantified changes in HFM. Results Of the 10 original HFM dimensions, seven were considered by clinical experts to be relevant in gene therapy (two dimensions not applicable to gene therapy; one overlapped with other dimensions).Experts agreed that each of the seven dimensions could be measured using existing clinical outcomes and PROs included in GENEr8-1, and agreed on an outcome and corresponding thresholds. Applying the thresholds to the GENEr8-1 trial data, the proportion of participants achieving HFM thresholds increased from baseline to Week 104 in each dimension. Increases ranged from+15% in the domains of ‘Joint Pain’ and ‘Affected Family Members and Caregivers’ to+42% in ‘Bleeding Benefit’ and+73% in ‘Injection Schedule’. Conclusion This is the first initiative to assess HFM using a visual multidimensional method, demonstrating that it is feasible to measure HFM in gene therapy clinical trials. Quantification may be further refined with future tool and methods development, and utilization of long-term data. The improvements observed among GENEr8-1 participants demonstrate progression towards HFM after administration of valoctocogene roxaparvovec. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany