Sustained effect of dirloctocogene samoparvovec gene therapy in hemophilia A

Gene therapy with dirloctocogene samoparvovec appears to remain well tolerated up to 7 years after administration, with sustained expression of factor VIII and a significant reduction in the number of bleeding events per year.

Dirloctocogene samoparvovec (SPK-8011) is an experimental gene therapy using an adeno-associated viral vector, developed for the treatment of hemophilia A. Previous results from a phase I/II study show that the gene therapy is well tolerated. In addition, participants showed consistent Factor VIII activity.

The results are now known after longer follow-up. In this study, 25 men with moderate to severe hemophilia A were treated with doses of 5 x 1011 vg/kg (n = 2), 1×1012 vg/kg (n = 3), 1.5 × 1012 vg/kg (n = 11) or 2 × 1012 vg/kg (n = 9). The average time since dosing was 220.6 weeks.

A total of 66 treatment-related adverse events occurred: 37 immunomodulation-related and 29 vector-related, including a serious grade 2 alanine aminotransferase (ALT) elevation. No thrombotic events occurred.

3 participants returned to prophylaxis. The median annualized bleeding rate (ABR) after derluctocogene samoparvovec was 0 versus 5.0 historically in participants who received prior prophylaxis (n=20), and 0.3 versus a historical ABR of 30.0 in participants who received “on-demand” treatment ( n=5).

source:

George LA, Croteau SE, Zhang T, et al. Long-term follow-up of participants in the phase I/II trial of derluctocogene samoparvovec (SPK-8011): durable FVIII expression and significant reduction in bleeding. ISTH 2024 Conference, Abstract OC 02.4.