RARE Daily

FDA Extends BioMarin’s Hemophilia A Gene Therapy PDUFA Target Action Date to June 30, 2023

March 7, 2023

Rare Daily Staff

BioMarin Pharmaceutical said it received notice from the U.S. Food and Drug Administration that the agency has extended review of the company’s Biologics License Application for Roctavian gene therapy for adults with severe hemophilia A.

The FDA determined that the submission of the three-year data analysis from the ongoing phase 3 GENEr8-1 study constituted a major amendment due to the substantial amount of additional data and set a new PDUFA target action date of June 30, 2023. The company had previously communicated that this data submission could be qualified as a major amendment. The FDA had completed a pre-license inspection of the manufacturing facility in early December 2022.

The phase 3 study, which included 134 participants, is the longest and largest to date for a gene therapy in hemophilia.

“We are continuing to work closely with FDA and appreciate the agency’s active engagement as we seek to deliver this important therapy to patients with severe hemophilia A,” said Hank Fuchs, president of Worldwide Research and Development of BioMarin. “The three-year data enhance our application and further reinforce our belief that Roctavian has the potential to fundamentally transform care for people with hemophilia A.”

Hemophilia A, also called Factor VIII deficiency or classic hemophilia, is an X-linked genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about one-third of cases are caused by a spontaneous mutation, a new mutation that was not inherited. Approximately 1 in 10,000 people have hemophilia A.

People living with hemophilia A lack sufficient functioning Factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. Additionally, people with the most severe form of hemophilia A (Factor VIII levels <1 percent) often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A make up approximately 50 percent of the hemophilia A population. Individuals with severe hemophilia A are treated with a prophylactic regimen of intravenous Factor VIII infusions administered 2-3 times per week or a bispecific monoclonal antibody that mimics the activity of Factor VIII administered 1-4 times per month. Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

The FDA has granted Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations to Roctavian (valoctocogene roxaparvovec). RMAT is an expedited program intended to facilitate development and review of regenerative medicine therapies, such as valoctocogene roxaparvovec, which are expected to address an unmet medical need in patients with serious conditions.

Roctavian has also received Orphan Drug designation from the European Medicines Agency (EMA) and FDA for the treatment of severe hemophilia A. The European Commission granted conditional marketing authorization to valoctocogene roxaparvovec gene therapy under the brand name Roctavian on August 24, 2022.

BioMarin has multiple clinical studies underway in its comprehensive gene therapy program for the treatment of severe hemophilia A. In addition to the global phase 3 study GENEr8-1 and the ongoing phase 1/2 dose escalation study, the company is also conducting a phase 3, single arm, open-label study to evaluate the efficacy and safety of valoctocogene roxaparvovec at a dose of 6e13 vg/kg with prophylactic corticosteroids in people with severe hemophilia A. Also ongoing is a phase 1/2 study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with pre-existing AAV5 antibodies and a phase 1/2 study with the 6e13 vg/kg dose of valoctocogene roxaparvovec in people with severe hemophilia A with active or prior Factor VIII inhibitors.

Photo: Hank Fuchs, president of Worldwide Research and Development of BioMarin

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