Treatment With Valoctocogene Roxaparvovec in a Patient With Severe Hemophilia A Led to Sustained Normal FVIII Levels

Valoctocogene roxaparvovec, an adeno-associated virus (AAV)-based gene therapy, enables endogenous factor VIII (FVIII) expression in patients with severe hemophilia A without the need for regular FVIII infusions. Long-term follow-up assesses durability, safety, and immune-related challenges following gene therapy.

Evaluation of six years of post-infusion outcomes of a patient receiving valoctocogene roxaparvovec, focusing on FVIII expression, immune response management, and adverse events (AEs).

A 44-year-old male with severe hemophilia A received a single infusion of valoctocogene roxaparvovec (6 × 10¹³ vector genomes/kg) in the GENEr8-1 study. Follow-up assessments included FVIII levels, liver function tests, and immune suppression management.

Post-infusion, the patient experienced an initial ALT elevation and FVIII decline, requiring oral prednisolone (60 mg/day) at week five. ALT elevation grade 3 (peaking at 555 U/L) was treated with intravenous methyl-prednisolone (week 6), followed by oral prednisolone. To mitigate cortisone side effects, prednisolone was switched to budesonide therapy at week 19 and continued for 6 months. FVIII activity (measured with a chromogenic FVIII assay) reached a peak of 202 IU/dL at month 6 and declined subsequently to levels of 50-70 IU/dL. After six years, FVIII activity remained normal, thus eliminating prophylactic FVIII infusions and bleeding episodes. A total of 20 AEs occurred, including two serious adverse events related to ALT elevation and a traumatic acetabulum fracture.

Valoctocogene roxaparvovec can offer durable FVIII expression in severe hemophilia A. This case provides valuable insights into personalised immunosuppression therapy with a favourable outcome for long-term efficacy and safety.