Investigational gene therapy for the treatment of patients with severe hemophilia A

BioMarin Pharmaceutical Inc. announced that has dosed the first patient in the global GENEr8-1 Phase III study with the 6e13 vg/kg dose for valoctocogene roxaparvovec (formerly BMN 270), an investigational gene therapy for the treatment of patients with severe hemophilia A. This is the first of two Phase III studies in the global Phase III program to dose a first patient.

The global Phase III program includes two studies with valoctocogene roxaparvovec, one with the 6e13 vg/kg dose (GENEr8-1) and one with the 4e13 vg/kg dose (GENEr8-2). Both Phase III GENEr8 studies will be open-label single-arm studies to evaluate the efficacy and safety of valoctocogene roxaparvovec. GENEr8-2 will enroll the first patient at the start of 2018. The primary endpoint in both studies will be based on the FVIII activity level achieved following valoctocogene roxaparvovec, and the secondary endpoints will measure annualized FVIII replacement therapy use rate and annualized bleed rate.

BioMarin will also begin a Phase 1/II Study with the 6e13kg/vg dose and with approximately 10 patients who are AAV5 positive. The first patient is expected to enroll in the first half of 2018.

Comment: Patients with hemophilia A are not able to produce enough functional Factor VIII to prevent bleeding and are currently treated with prophylactic or on-demand infusions of plasma-derived or recombinant Factor VIII. BMN 270 is designed to address the underlying genetic defect that prevents the expression of functional Factor VIII by using an adeno-associated virus (AAV) vector to deliver a functional copy of the factor VIII gene to a patients' own cells with the aim of a single infusion of BMN 270 providing a long-lasting increase in Factor VIII levels.