There have been marked advancements in the treatment of hemophilia A over the past decades.  Adoption of routine prophylaxis to prevent bleeding as the standard of care has led to many children growing into adulthood with normal joint function and adults with improved function and quality of life.  However, there remains a continued treatment burden and bleeding events, including spontaneous hemorrhage. Newer therapeutics with regulatory approval and in late phase clinical trial may further decrease the treatment burden and improve efficacy.  This session will provide an update on gene therapy for hemophilia and discuss gene therapy in the context of new and coming therapies. 

Frank W.G. Leebeek, MD, PhD
The Promise of Gene Therapy for Severe Hemophilia A

In the past decade enormous improvements have been made in delivering AAV-based gene therapy in patients with hemophilia A. In several phase 1 and 3 studies patients reached normal levels of FVIII after a single dose of AAV-delivered FVIII-gene construct, leading to reduced bleeding rates and patients could stop regular FVIII prophylaxis. During follow up of more than five years FVIII activity declined over time, however the majority of patients still have residual FVIII expression enabling them to refrain for prophylaxis. These promising results led to FDA and EMA approval of gene therapy for hemophilia A in 2022.  Longer term follow-up is needed to show us the duration of benefits and (potential) drawbacks of gene therapy compared to current and other novel treatments.

Christine L Kempton, MD, MSc
Unknowns of Gene Therapy and Successes of Medical Therapies for Hemophilia A

Although gene therapy has held the promise of a cure, a consistent cure has yet to be realized. Additionally, the beneficial results seen in hemophilia A gene therapy clinical trials have occurred with meaningful challenges. This talk will review the risks and benefits of gene therapy for hemophilia A and consider them within the context of therapies (emicizumab and Fc-VWF-XTEN fusion protein-eht) that have shown consistent benefit compared with previously available factor VIII products as well as other promising therapies (Mim8, fitusiran, concizumab, and marstacimab) in late-stage clinical trials.