FDA Accepts BLA for Hemophilia A Gene Therapy


If approved, valoctocogene roxaparvovec would be the first gene therapy in the U.S. for the treatment of severe hemophilia A. A PDUFA action date has been set for March 31, 2023.

The FDA has accepted the resubmission of BioMarin Pharmaceutical’s biologics license application (BLA) for the AAV gene therapy, valoctocogene roxaparvovec, for adults with severe hemophilia A. If approved, valoctocogene roxaparvovec would be the first gene therapy in the U.S. for the treatment of severe hemophilia A.

The Prescription Drug User Fee Act (PDUFA) target action date is March 31, 2023, but company officials indicated the FDA may extend the review time to assess additional long-term follow-up data.

The company had resubmitted the BLA early in October 2022. The FDA had issued a complete response letter for valoctocogene roxaparvovec in August 2020 requesting 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.

Hank Fuchs, M.D.

Hank Fuchs, M.D.

“In this application, we have provided a substantial body of evidence that supports the safe and effective use of valoctocogene roxaparvovec for the treatment of adults with severe hemophilia A,” Hank Fuchs, M.D., president of worldwide research and development at BioMarin, said in a press release. “In addition, we have proposed 15 years of follow-up for all clinical study participants, as well as a post-approval registry study to follow patients dosed in a real-world setting, to further characterize long-term effects on safety and efficacy that will contribute to increasing the body of knowledge of AAV gene therapy in severe 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; incidence is estimated at 1 in 4,000-5,000 male births. The current standard of care 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.

Although no price has been provided by BioMarin, the Institute for Clinical and Economic Review (ICER) used a placeholder price of $2.5 million for the one-time therapy when it released a draft evidence report in September 2022. ICER analysts found the gene therapy would provide cost savings and projected gains in quality adjusted life years. ICER calculated the lifetime cost of managing hemophilia A among clinically eligible patients using 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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