Multiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A

   This phase 1–2 clinical trial investigated SPK-8011, an adeno-associated viral (AAV) vector designed to promote hepatocyte expression of factor VIII in adult men with hemophilia A. Among 18 participants receiving varied vector doses, 16 maintained sustained factor VIII expression over a multi-year follow-up, resulting in a 91.5% reduction in annualized bleeding rates and elimination of prophylactic therapy. Two participants lost expression due to immune responses. The study found no major safety concerns, with mild elevations in liver enzymes being the most common adverse event. Expression levels were stable over time, with peak factor VIII activity occurring between weeks 6 to 12. The results support SPK-8011’s potential as a durable gene therapy strategy.

   This phase 1–2 clinical trial investigated SPK-8011, an adeno-associated viral (AAV) vector designed to promote hepatocyte expression of factor VIII in adult men with hemophilia A. Among 18 participants receiving varied vector doses, 16 maintained sustained factor VIII expression over a multi-year follow-up, resulting in a 91.5% reduction in annualized bleeding rates and elimination of prophylactic therapy. Two participants lost expression due to immune responses. The study found no major safety concerns, with mild elevations in liver enzymes being the most common adverse event. Expression levels were stable over time, with peak factor VIII activity occurring between weeks 6 to 12. The results support SPK-8011’s potential as a durable gene therapy strategy.