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

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

To address the issues raised in the CRL, the resubmitted BLA includes 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 a  post-approval registry study to follow patients in a real-world setting.

A Prescription Drug User Fee Act target action date of March 31, 2023 has been set for this application.

“In this application, we have provided a substantial body of evidence that supports the safe and effective use of valoctocogene roxaparvovec for the treatment of adults with severe hemophilia A. In addition, we have proposed 15 years of follow-up for all clinical study participants, as well as a post-approval registry study to follow patients dosed in a real-world setting, to further characterize long-term effects on safety and efficacy that will contribute to increasing the body of knowledge of AAV gene therapy in severe hemophilia A.” said Hank Fuchs, MD, President of Worldwide Research and Development at BioMarin.

Reference

FDA accepts BioMarin’s Biologics License Application (BLA) for valoctocogene roxaparvovec AAV gene therapy for adults with severe hemophilia A. News release. BioMarin Pharmaceutical Inc. October 12, 2022. Accessed October 13, 2022. https://www.prnewswire.com/news-releases/fda-accepts-biomarins-biologics-license-application-bla-for-valoctocogene-roxaparvovec-aav-gene-therapy-for-adults-with-severe-hemophilia-a-301647823.html