OC 01.2 - Improvements in Health-Related Quality of Life in Adults with Severe or Moderately Severe Hemophilia B After Receiving Etranacogene Dezaparvovec Gene Therapy

Background: Despite current prophylactic therapy for hemophilia B, breakthrough bleeding still occurs negatively affecting health-related quality of life (HRQoL). The pivotal Phase 3 HOPE-B trial of the investigational AAV gene transfer product, etranacogene dezaparvovec, demonstrated sustained factor IX (FIX) activity and bleed protection superior to FIX concentrate prophylaxis.

Aims: Here we report the impact on HRQoL.

Methods: Fifty-four adults with hemophilia B (FIX≤2%) received standard of care FIX concentrate prophylaxis in the 6-month lead-in period followed by a single infusion of etranacogene dezaparvovec. HRQoL was assessed with the hemophilia-specific Hem-A-QoL during the lead-in and at 6 and 12 months after etranacogene dezaparvovec. Repeated measures linear mixed models estimated the difference in scores before and after gene therapy. A one-sided p-value ≤0.025 for the post-treatment, lead-in period was considered statistically significant. The analyses were not adjusted for multiplicity.

Results: Significant model-based mean differences in scores and the percentage improvement compared with the lead-in period were as follows: Total Score (least square (LS) mean -5.50; p< 0.0001; 21.5%), domains ‘Treatment’ (LS mean -14.88; p< 0.0001; 59.0%), ‘Feelings’ (LS mean -9.42; p< 0.0001; 45.7%), ‘Future’ (LS mean -5.02; p=0.0023; 16.2%) ‘Work/School’ (LS mean -4.99; p=0.0036; 28.8%). The p-value was slightly above the p< 0.025 threshold for the ‘Physical Health’ domain (LS mean -4.21; p=0.0278; 13.5%). Results were not significant for the five remaining Hem-A-QoL domains. ‘Treatment’ reflects how burdened patients are by their hemophilia treatments. ‘Feelings’ reflects current emotions associated with having hemophilia. ‘Future’ reflects concerns about how hemophilia will affect their life plans. ‘Work/School’ reflects how well patients think they perform these responsibilities.

Conclusion(s): HRQoL improvements after gene therapy demonstrate that etranacogene dezaparvovec can reduce the burden associated with hemophilia and FIX prophylactic therapy. This may contribute to how hemophilia B patients view their work/school performance as well as providing a sense of optimism for the future.