BioMarin Resubmits BLA for Hemophilia A Gene Therapy


If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the United States for the treatment of severe hemophilia A.

BioMarin Pharmaceutical has resubmitted a biologics license application (BLA) to the FDA for its investigational adeno-associated virus vector gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A.

The resubmission incorporates the company’s response to the FDA complete response letter for valoctocogene roxaparvovec gene therapy issued on Aug. 18, 2020, including two-year outcomes from the global GENEr8-1 phase 3 study and supportive data from five years of follow-up from the ongoing phase 1/2 dose escalation study.

BioMarin anticipates an FDA response by the end of October on whether the BLA resubmission is complete and acceptable for review. Typically, BLA resubmissions are followed by a six-month review procedure. However, company executives anticipate an additional three months of review. If approved, valoctocogene roxaparvovec would be the first commercially-available gene therapy in the United States for the treatment of severe hemophilia A.

Hank Fuchs, M.D.

Hank Fuchs, M.D.

“This large and robust data set provided in this BLA resubmission shows an encouraging efficacy profile,” Hank Fuchs, M.D., president of worldwide research and development at BioMarin, said in a press release. “We remain committed to sharing these data with the public, along with even longer-term data generated through our ongoing clinical trials and any post-approval studies, to further our understanding of AAV gene therapy in severe hemophilia A and of gene therapies more broadly.”

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; incidence is estimated at 1 in 4,000-5,000 male births. The current standard of care for most hemophilia A patients who are severely affected today is a prophylactic regimen of intravenous infusions three times per week.

BioMarin’s gene therapy uses an adeno-associated virus vector to deliver a functional gene to the cells in the liver that is designed to enable the body to produce Factor VIII on its own without the need for continued hemophilia prophylaxis.

In the phase 1/2 study, the safety profile of valoctocogene roxaparvovec was consistent with previously reported data with no delayed-onset treatment related adverse events. All participants continue to remain off corticosteroids since the first year. No participants developed inhibitors to Factor VIII, and no participants withdrew from the study.No participants have developed thrombotic events.

The most common adverse occurred early after a single infusion and included short-lived infusion-associated reactions and transient, asymptomatic, and mild to moderate rise in the levels of certain proteins and enzymes measured in liver function tests with no long-lasting clinical sequelae.

In a draft evidence report, the Institute for Clinical and Economic Review (ICER) found that valoctocogene roxaparvovec at an assumed placeholder price of $2.5 million would provide cost savings and projected gains in quality adjusted life years. The draft evidence report is now open for public comment, with a final report expected near the end of the year.

ICER calculated the lifetime cost of managing hemophilia A among clinically eligible patients using one-time administration with valoctocogene roxaparvovec versus emicizumab prophylaxis. Total costs in the model include treatment, treatment-related adverse events, treatment for bleeding episodes, arthropathy, surgery, and non-drug costs. ICER assumed annual cost of emicizumab to be $640,000 per year and one-time valoctocogene roxaparvovec price to be $2.5 million.

The European Commission granted conditional marketing authorization to valoctocogene roxaparvovec gene therapy under the brand name Roctavian on Aug. 24, 2022, and endorsed the recommendation from the European Medicines Agency (EMA) to maintain orphan drug designation, thereby granting a 10-year period of market exclusivity in the European Union.

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