Impact of Gene Therapy on the Haemophilia‐Free Mind: Outcomes Before and After Valoctocogene Roxaparvovec in GENEr8‐1 Trial Participants

ABSTRACT Introduction Haemophilia‐free mind is an aspirational concept defined as a state in which affected individuals are liberated from physical, mental, and treatment burdens of haemophilia. A conceptual framework has been proposed for the haemophilia‐free mind that comprises ten dimensions. Aim To evaluate changes in achievement towards a haemophilia‐free mind in participants with haemophilia A who received valoctocogene roxaparvovec gene therapy in the GENEr8‐1 trial (NCT03370913), by confirming relevant dimensions, with measures and thresholds for each. Methods An expert panel comprising four haemophilia clinicians and one patient expert identified dimensions of the haemophilia‐free mind relevant to gene therapy. Measures and thresholds were defined for each dimension and used to analyse GENEr8‐1 data to determine the proportion of participants achieving these thresholds at Baseline and Week 208. Results The expert panel confirmed 7/10 dimensions as appropriate for use in gene therapy trials and defined measurement thresholds for each dimension. Among GENEr8‐1 trial participants, improvements were observed across all seven dimensions. The proportion of participants with zero treated bleeds increased from 33% (Baseline) to 54% (Week 208). Similarly, those reporting no exogenous factor VIII use rose from 0% to 33%. Improvements in perceived burden on family members, physical activity, and travel were 8%, 16%, and 18%, respectively. Conclusion This expert‐led analysis demonstrates application of the haemophilia‐free mind framework to clinical trial data using existing outcome measures. Mapping GENEr8‐1 data to this framework demonstrated improvements of up to 33% in domains that contribute towards a haemophilia‐free mind in participants after valoctocogene roxaparvovec treatment.