Rare Disease AdvisorGene Therapy Shows Long-Term Efficacy in Hemophilia A

Read the original article

A phase 1/2 trial published in Haemophilia demonstrates the long-term efficacy and safety of valoctocogene roxaparvovec gene therapy for severe hemophilia A. The study, conducted over 6-7 years, shows sustained hemostatic control in most participants, with significant reductions in bleeding episodes and factor VIII (FVIII) use. These findings provide important insights into the potential of gene therapy as a treatment option for patients with severe hemophilia A.

Key Points:

• The trial included male participants aged 18 or older with severe hemophilia A, no history of FVIII inhibitors, or anti-AAV5 antibodies.
• Two cohorts received different doses: 6×10¹³ vg/kg (n=7, 7-year follow-up) and 4×10¹³ vg/kg (n=6, 6-year follow-up).
• Mean annualized treated bleeds and exogenous FVIII infusion rates remained over 88% lower than baseline values throughout the study.
• Mean FVIII activity levels were 16.2 IU/dL in the 6×10¹³ vg/kg cohort and 6.7 IU/dL in the 4×10¹³ vg/kg cohort, corresponding to mild hemophilia levels.
• Regression analyses showed a gradual decline in FVIII activity: -0.001 IU/dL per week (6×10¹³ cohort) and -0.07 IU/dL per week (4×10¹³ cohort).
• Treatment-related adverse events were minimal in the last year, with no participants developing FVIII inhibitors.
• Two patients in the 6×10¹³ vg/kg cohort resumed prophylaxis due to significant bleeding events.

HCN Medical Memo
The long-term efficacy and safety data from this phase 1/2 trial of valoctocogene roxaparvovec gene therapy for severe hemophilia A are promising. Although some patients may still require prophylaxis, the overall reduction in bleeding episodes and factor VIII use suggests that this treatment could significantly improve quality of life for many patients with severe hemophilia A. As gene therapy continues to evolve, it may become an important tool in managing this chronic condition.

More on Hemophilia