Among patients with severe hemophilia A, valoctocogene roxaparvovec, a novel gene therapy, appears to reduce the risk of bleeding and rate of factor VIII (FVIII) infusion, according to research presented at the International Society on Thrombosis and Haemostasis (ISTH) 2021 Virtual Congress.

Valoctocogene roxaparvovec, which relies on a viral vector, transfers FVIII-SQ to hepatocytes, which increases FVIII production among patients with hemophilia A. For this open-label, single-arm phase 3 trial (GENEr8-1; Identifier: NCT03370913), researchers evaluated the safety and efficacy of valoctocogene roxaparvovec in this patient population.

All included patients had severe hemophilia A, which was defined as FVIII levels of 1 IU/dL or lower. The study’s primary endpoint was median FVIII activity change from baseline. Secondary endpoints included changes in bleeding rates and FVIII infusion rates.

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Overall, 134 participants were enrolled and completed the target treatment period; the median patient age was 30 years (range, 18-70). Among the 132 patients who were human immunodeficiency virus (HIV)-negative, chromogenic FVIII levels increased by a mean 41.9 IU/dL by weeks 49 to 52.

In 112 patients who were rolled over from a non-interventional study, the mean annualized bleeding rates decreased by 84% at week 4, while FVIII infusion rates decreased by 99%. While 36 (32.1%) of these patients had 0 bleeds at baseline, 89 patients (79.5%) recorded 0 bleeds by week 4.

A total of 22 patients (16.4%) had a serious adverse event (AE); alanine aminotransferase elevations occurred in 86% of the entire cohort, although 95.6% of these cases were resolved. Other common AEs included headache (38%), nausea (37%), and elevated aspartate aminotransferase (35%).

“In the largest-to-date hemophilia gene therapy trial, valoctocogene roxaparvovec yielded meaningful endogenous FVIII expression in participants with severe hemophilia A, resulting in significant decreases in bleeding and FVIII infusion,” the authors wrote.


Ozelo MC, Mahlangu J, Pasi K, et al. Efficacy and safety of valoctocogene roxaparvovec adeno-associated virus gene transfer for severe hemophilia A: results from the phase 3 GENEr8-1 trial. Paper presented at: International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress; July 17-21, 2021; virtual. Abstract OC 26.1.