The Biologics License Application (BLA) for valoctocogene roxaparvovec, an investigational adeno-associated virus (AAV) gene therapy, has been resubmitted to the Food and Drug Administration (FDA) for the treatment of hemophilia A in adults.

Valoctocogene roxaparvovec is administered as a single infusion to produce clotting factor VIII. BioMarin originally submitted the BLA in December 2019, which included interim analysis from the phase 3 GENEr8-1 study ( Identifier: NCT03370913) and 3-year phase 1/2 data ( Identifier: NCT02576795).

The FDA subsequently issued a Complete Response Letter (CRL) in August 2020 requesting the Company provide substantial evidence from its phase 3 study demonstrating durable effect using annualized bleeding rate (ABR) as the primary endpoint. 

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To address the issues raised in the CRL, the Company provided 2-year outcomes from the GENEr8-1 study and supportive data from 5 years of follow-up from the 6e13 vg/kg dose cohort in the ongoing phase 1/2 dose escalation study. 

Additional data from GENEr8-1 showed stable and durable bleed control, along with a reduction in mean ABR and mean annualized Factor VIII infusion rate. The Company also proposed a long-term extension study to follow all clinical trial participants for up to 15 years and 2 post-approval registry studies in the resubmitted application.

“We are pleased to reach this point in the development program for valoctocogene roxaparvovec and look forward to working with the FDA with the goal of bringing a potentially transformative therapy to people with severe hemophilia A in the United States,” said Hank Fuchs, MD, President of Worldwide Research and Development at BioMarin. “This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile. 


BioMarin resubmits Biologics License Application (BLA) for valoctocogene roxaparvovec aav gene therapy for severe hemophilia A to the FDA. News release. BioMarin Pharmaceutical Inc. Accessed September 29, 2022.

This article originally appeared on MPR