BioMarin resubmits BLA for bleeding disorder gene therapy

Sept. 30, 2022

California-based BioMarin Pharmaceutical is not giving up on its investigational AAV gene therapy for hemophilia A just yet, announcing this week that it resubmitted a Biologics License Application (BLA) to the FDA.

The FDA granted the drug — called valoctocogene roxaparvovec — Regenerative Medicine Advanced Therapy (RMAT) designation in 2021. RMAT is complementary to Breakthrough Therapy Designation, and the drug also holds orphan designation.

In its resubmission, BioMarin addresses its concerns raised by an FDA’s complete response letter issued in 2020, including two-year outcome data from its GENEr8-1 phase 3 trial as well as five-year follow-up data from the previous studies. In the original letter, the FDA said that results from the phase 1/2 trials and phase 3 trials had conflicting results as to the protective durability of the drug. 

Patients with Hemophilia A suffer mutations in the F8 gene which has the instructions for a protein that is crucial to adequate clotting, so oftentimes they produce an ineffective version of the protein, if any at all. The drug delivers instructions for the protein as well as transfects a functional version of the gene into liver cells. 

BioMarin says that they expect to hear if the BLA is complete and accepted by the end of October. After receiving this notification, the company expects for it to be a minimum of another six months before approval, which is the typical review time for BLA resubmissions.