BioMarin Reports Phase 3 Cohort of Valoctocogene Roxaparvove Meets Pre-Specified Endpoint; Regulatory Submissions Planned in U.S. and Europe

 BioMarin announced valoctocogene roxaparvovec, a gene therapy for adults with severe hemophilia A, achieved pre-specified clinical criteria for regulatory review in the U.S. and Europe in the phase 3 cohort of the GENEr8-1 study.

GENEr8-1 is an open label, single arm study evaluating a 6e13 vg/kg dose. The primary endpoint is based on the FVIII activity level achieved following valoctocogene roxaparvovec administration. As of the April 30, 2019 data cutoff, between weeks 23 to 26, in a cohort of the Phase 3 GENEr8-1 study of valoctocogene roxaparvovec dosed at 6e13 vg/kg, seven of 16 study subjects reached or exceeded the pre-specified Factor VIII levels of 40 international units per deciliter using the chromogenic substrate (CS) assay.  Subsequent to the April 30 cutoff, one additional subject met that criteria, bringing the total to eight subjects. For the 16 patients who had reached week 26 by the April 30 cutoff since administration of valoctocogene roxaparvovec, the estimated median Annual Bleed Rate (ABR) was zero and the estimated mean ABR was 1.5, representing a reduction of 85% from baseline levels where all patients were on standard of care prophylaxis.  In addition, there was an 84% reduction in median annualized Factor VIII usage and a 94% reduction in mean FVIII usage annualized between week 5 and 26.  In the 23 to 26 week time period the mean Factor VIII level using the CS assay was 36 (SD=28) IU/dL and the median was 33 IU/dL.

The company plans to meet with the U.S. FDA and European Medicines Agency (EMA) to review the phase 3 data and the other elements of a submission and intends to announce the timing for its planned marketing applications in 3Q 2019.

The U.S FDA has granted valoctocogene roxaparvovec Breakthrough Therapy Designation. The EMA has granted access to its Priority Medicines (PRIME) regulatory initiative for valoctocogene roxaparvovec. Both the FDA and EMA have granted Orphan Drug Designation for the treatment of severe hemophilia A.

About hemophilia A

Hemophilia A is a genetic disease caused by the deficiency of clotting factor VIII. It is the most common type of hemophilia and occurs much more frequently in males; the incidence is estimated at 1 in 4,000-5,000 male births. People born with hemophilia produce little or no clotting factors and are missing or have low levels of clotting factor VIII. These proteins work with platelets in the clotting process. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding. Many patients with hemophilia experience spontaneous bleeding events that result in progressive and debilitating joint damage.

About valoctocogene roxaparvovec

Valoctocogene roxaparvovec is a gene therapy using an AAV-factor VIII vector. In mouse models of hemophilia A, valoctocogene roxaparvovec restored factor VIII plasma concentrations to levels projected to be adequate for normal clotting in humans.