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Jennifer Quinn,1 Kathleen A Delaney,2 Wing Yen Wong,2 Wolfgang Miesbach,3 Monika Bullinger4 1BioMarin Pharmaceuticals UK Ltd, London, UK; 2BioMarin Pharmaceutical Inc., Novato, CA, USA; 3Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany; 4Department of Medical Psychology, University Medical Center Hamburg Eppendorf, Hamburg, GermanyCorrespondence: Jennifer Quinn, BioMarin Pharmaceuticals UK Ltd, 10 Bloomsbury Way, London, WC1A 2SL, UK, Tel +44 7976 129 039, Email jennifer.quinn@bmrn.comPurpose: The hemophilia-specific health-related quality of life (HRQOL) questionnaire (Haemo-QOL-A) is validated for detecting QOL changes following standard therapy for hemophilia A, but has not been rigorously evaluated after gene therapy. This post hoc analysis evaluated the psychometric properties of Haemo-QOL-A in adult people with severe hemophilia A (PWSHA) receiving valoctocogene roxaparvovec (AAV5-hFVIII-SQ) in 2 clinical trials (phase 1/2, NCT02576795; phase 3, NCT03370913).Patients and Methods: Adult PWSHA (factor VIII levels ≤ 1 IU/dL) received 1 AAV5-hFVIII-SQ infusion (6× 1013 vg/kg). Participants were assessed using the Haemo-QOL-A and the EuroQOL (EQ)-5D-5L and visual analog scale (VAS) questionnaires pre- and post-infusion. Psychometric analyses included convergent and discriminant validity, internal consistency, and reliability. Clinically important difference (CID) was estimated using 3-point change in EQ-5D-5L VAS as anchor.Results: Haemo-QOL-A data were analyzed from 7 (phase 1/2, 3-year follow-up) and 16 participants (phase 3, 26-week analysis). Change in Haemo-QOL-A Total Scores correlated with EQ-5D-5L VAS score change at 26 weeks (Pearson’s correlation 0.77). At 26 weeks, increased Haemo-QOL-A Physical Functioning was associated with decreased EQ-5D-5L Pain and Discomfort and decreased Anxiety and Depression (Spearman’s Rank correlations − 0.73 and − 0.62, respectively, P < 0.01). Internal consistency analysis showed good reliability for all domains (Cronbach’s alpha > 0.7) except Treatment Concern (Cronbach’s alpha = 0.31). Anchor-based CID estimates were met for Haemo-QOL-A Total Score (≥ 5.5) and domain scores (≥ 6) for Consequences of Bleeding, Physical Functioning, Role Functioning, and Worry.Conclusion: Our preliminary results suggest that the Haemo‐QOL‐A is a valid, reliable instrument for HRQOL assessment in PWSHA undergoing gene therapy. Future research should be undertaken to confirm these findings in a larger number of participants.Keywords: severe hemophilia A, gene therapy, quality of life, Haemo-QOL-A, psychometric testing, clinically important difference

Wolfgang Miesbach,1 Robert Klamroth2 1Medical Clinic 2, Institute of Transfusion Medicine, University Hospital, Frankfurt, Germany; 2Department for Internal Medicine, Vascular Medicine and Coagulation Disorders, Vivantes Klinikum im Friedrichshain, Berlin D - 10249, GermanyCorrespondence: Wolfgang MiesbachMedical Clinic 2, Institute of Transfusion Medicine, University Hospital, Frankfurt, GermanyTel +49 69 6301-5051Email wolfgang.miesbach@kgu.deBackground: The phase ½ hemophilia B clinical trial (AMT-060) demonstrated stable endogenous FIX levels after 3.5 years (mean FIX activity between 5.1% and 7.5%) with continued reductions in annualized bleeds to near zero with the higher dose, and a 78– 96% reduction by year in exogenous FIX use.Objective: The views of all the three participants from Germany participating in the AMT-060 study have been investigated about their experiences with conventional and gene therapy and the effects of the forms of therapy on everyday life.Patients/Methods: The patients (aged 33– 35 years) performed regular prophylactic replacement with factor IX concentrate prior to the gene therapy, reported 0– 7 bleeds in the year prior to the treatment, with Hemophilia Joint Health Scores of 0– 8. Following topics have been investigated “dealing with illness”, “participation in studies”, “perception of conventional therapy”, “perception of gene therapy”, “significance of participation in gene therapy studies”, “therapy of haemophilia after the end of the study”.Results: All three participants have started to become more active and do more sports. However, they expressed anxiety about not knowing how long the effect would last and they felt that psychological support would be needed if the factor IX level fell back in the future. No patient expressed concern about any long-term potential negative consequences of gene therapy.Conclusion: Gene therapy has the potential to change the life of patients with haemophilia not only by the reduction of bleeding events but also by the increase of active and sportive activities.Keywords: gene therapy, haemophilia, patient experience, patient interview