In two single-arm phase 3 trials, gene therapy was effective in reducing bleeding at ≈2 years, but questions about long-term durability and safety remain.
Advances in adeno-associated virus 5 (AAV5) vector gene delivery platforms and genome designs have led to development of efficient gene therapy for hemophilia A and hemophilia B. Now, two industry-funded, open-label, single-arm, multicenter, phase 3 trials show promising results with longer follow-up.
In the GENEr8-1 study, 134 men with severe hemophilia A (factor VIII <1%) who were receiving factor VIII prophylaxis were given a single infusion of valoctocogene roxaparvovec, an investigational therapy. The mean annualized rate of treated bleeding events decreased by 84.5% from baseline to 2 years after the infusion (P<0.001). Factor VIII utilization decreased by 98.2%. The estimated transgene-derived half-life of factor VIII production was 1…
Reviewing Author
DisclosuresConsultant/Advisory BoardGenentech
Grant/Research SupportX4 Pharma; Pfizer; Health Resources and Services Administration; American Thrombosis and Hemostasis Network/CDC; Carver College of Medicine
Leadership Positions in Professional SocietiesInternational Society on Thrombosis and Haemostasis (Finance Committee Member); American Society of Hematology Clinical Research Translational Institute
DisclosuresConsultant/Advisory BoardGenentech
Grant/Research SupportX4 Pharma; Pfizer; Health Resources and Services Administration; American Thrombosis and Hemostasis Network/CDC; Carver College of Medicine
Leadership Positions in Professional SocietiesInternational Society on Thrombosis and Haemostasis (Finance Committee Member); American Society of Hematology Clinical Research Translational Institute