ABSTRACT Introduction 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. Aim 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). Methods A 44‐year‐old male with severe hemophilia A received a single infusion of valoctocogene roxaparvovec (6 × 10 13 vector genomes/kg) in the GENEr8‐1 study. Follow‐up assessments included FVIII levels, liver function tests, and immune suppression management. Results 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. Conclusion 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.
Herbst et al. (Thu,) studied this question.