On Aug. 24, 2022, BioMarin Pharmaceutical announced that the European Commission (EC) has granted conditional marketing authorization (CMA) to ROCTAVIAN™ (valoctocogene roxaparvovec) gene therapy for the treatment of severe hemophilia A (congenital Factor VIII deficiency) in adult patients without a history of Factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5). The EC also endorsed EMA’s recommendation for Roctavian to maintain orphan drug designation, thereby granting a 10-year period of market exclusivity.  The EMA recommendation noted that, even in light of existing treatments, Roctavian may potentially offer a significant benefit to those affected with severe Hemophilia A.  The one-time infusion is the first approved gene therapy for hemophilia A and works by delivering a functional gene that is designed to enable the body to produce Factor VIII on its own without the need for continued hemophilia prophylaxis, thus relieving patients of their treatment burden relative to currently available therapies. People with hemophilia A have a mutation in the gene responsible for producing Factor VIII, a protein necessary for blood clotting.

It is estimated that more than 20,000 adults are affected by severe hemophilia A across more than 70 countries in Europe, the Middle East, and Africa. Of the 8,000 adults with severe hemophilia A in the 24 countries within BioMarin’s footprint covered by today’s EMA approval, there are an estimated 3,200 patients who will be indicated for Roctavian. BioMarin anticipates additional access to ROCTAVIAN™ for patients outside of the EU through named patient sales based on the European Medicines Agency (EMA) approval in countries in the Middle East, Africa and Latin America and expects additional market registrations to be facilitated by the EMA license.

The EC based its decision on a significant body of data from the Roctavian clinical development program, the most extensively studied gene therapy for hemophilia A, including two-year outcomes from the global GENEr8-1 Phase 3 study.  The GENEr8-1 Phase 3 study demonstrated stable and durable bleed control, including a reduction in the mean annualized bleeding rate (ABR) and the mean annualized Factor VIII infusion rate.  In addition, the data included five and four years of follow-up from the 6e13 vg/kg and 4e13 vg/kg dose cohorts, respectively, in the ongoing Phase 1/2 dose escalation study. BioMarin has committed to continue working with the broader community and the EMA to monitor the long-term effects of treatment.  The Product Information will be available shortly on the EMA website under the Medicines tab.  Search for “ROCTAVIAN” and select “Human medicine European public assessment report (EPAR):  Roctavian.  Then select “Product Information” in the Table of Contents and then select “Roctavian: EPAR – Product Information.”

A Conditional Marketing Authorization (CMA) recognizes that the medicine fulfils an unmet medical need based on a positive benefit-risk assessment, and that the benefit to public health of the immediate availability on the market outweighs the uncertainties inherent to the fact that additional data are still required. BioMarin will provide further data from ongoing studies within defined timelines to confirm that the benefits continue to outweigh the risks, building on what already constitutes the largest clinical data package for gene therapy in hemophilia A. Conversion to a standard marketing authorization will be contingent on the provision of additional data from currently ongoing Roctavian clinical studies, including longer-term follow up of patients enrolled in the pivotal trial GENEr8-1, as well as a study investigating efficacy and safety of ROCTAVIAN with prophylactic use of corticosteroids (Study 270-303), for which enrollment is now complete.

Orphan drug designation is reserved for medicines treating rare (affecting not more than five in 10,000 people in the EU), life-threatening or chronically debilitating diseases.  Authorized orphan medicines benefit from ten years of market exclusivity, protecting them from competition with similar medicines with the same therapeutic indication, which cannot be marketed during the exclusivity period.