RARE Daily

FDA Grants BioMarin Priority Review for Hemophilia A Gene Therapy

February 21, 2020

Rare Daily Staff

The U.S. Food and Drug Administration has accepted BioMarin Pharmaceutical’s biologics license application for its investigational AAV5 gene therapy, valoctocogene roxaparvovec, for adults with hemophilia A, and granted it Priority Review. 

The marketing application is the first to be accepted by the FDA for a gene therapy product for any type of hemophilia.

Priority review is granted to drugs that treat a serious condition and if approved would provide a significant improvement in safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. The FDA is expected to act on the application by August 21, 2020. 

The agency also accepted a premarket approval application for a companion diagnostic test produced by ARUP Laboratories to assess preexisting immunity to the AAV5 vector, which would make a person with hemophilia ineligible for the AAV5-mediated gene therapy treatment. BioMarin estimates that approximately 80 percent of people with hemophilia A in the United States do not have preexisting immunity to the viral vector it uses to deliver the gene therapy.

People living with hemophilia A lack enough factor VIII protein to help their blood clot and are at risk for painful and potentially life-threatening bleeds from even modest injuries. In cases where the condition is severe, people with hemophilia A experience painful, spontaneous bleeds into their muscles or joints. Even with the use of replacement factor VIII therapy, many people continue to experience bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

BioMarin’s experimental gene therapy valoctocogene roxaparvovec, also known as valrox, is an AAV-factor VIII gene therapy designed to restore adequate levels of factor VIII for normal clotting. The therapy is being developed as a one-time treatment for adults with severe hemophilia A and could eliminate the need for ongoing factor VIII treatments. The standard of care for most hemophilia A patients who are severely affected today is a regimen of intravenous infusions three times per week.

BioMarin’s application is based on updated three-year phase 1/2 data and the recently completed phase 3 interim analysis of patients treated with material from its soon-to-be-commercialized gene therapy manufacturing process.

“Valoctocogene roxaparvovec has the potential to be the first gene therapy approved in any type of hemophilia and the acceptance of this application and its priority review status marks a significant milestone for gene therapies in general and for the hemophilia community specifically,” said Hank Fuchs, president of global research and development at BioMarin. 

The FDA told BioMarin that they are not currently planning to hold an advisory committee meeting to discuss the application.  

There had been concern, when the registrational data was first reported in May 2019, about the durability of the therapy, which showed factor VIII levels falling in the second year of treatment, but BioMarin said the data suggested that factor VIII levels would approach a plateau sufficient to not require infusions to prevent bleeds.

“The hemophilia community has been waiting for decades for gene therapies,”  said Doris Quon, medical director, Orthopaedic Hemophilia Treatment Center at The Orthopaedic Institute for Children. “The FDA acceptance of the filing and initiation of review for the first gene therapy for hemophilia A builds on years of scientific achievements in improving the standard of care for people with bleeding disorders,”

Valrox has Breakthrough Therapy and Orphan Drug designations from the FDA and the European Medicines Agency (EMA), and Priority Medicines (PRIME) designation in the European Union. BioMarin’s marketing application for valrox is currently under accelerated review by the EMA.

Photo: Hank Fuchs, president, Global Research and Development at BioMarin.

Stay Connected

Sign up for updates straight to your inbox.