FDA Recommends Additional Data for BioMarin’s Investigational Gene Therapy

Biomarin announced that they received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) on August 18th for their investigational hemophilia A gene therapy valoctocogene roxaparvovec. The CRL indicates that while the review cycle for the Biologics License Application (BLA) for valoctocogene roxaparvovec is complete, the application, in present form, is not ready for approval. The crux of the letter is the introduction of a new recommendation that is focused on acquiring additional safety and efficacy data.

The recommendation came as a surprise to BioMarin, as it introduces BLA-supporting data endpoints beyond what the company and the FDA had previously agreed upon. The CRL specifically recommends two years of data from BioMarin’s ongoing 270-301 (phase 3) study to provide “substantial evidence” of a durable effect using annualized bleeding rate as the primary endpoint. According to the BioMarin press release, the agency had concluded that the differences between study 270-201 (phase 1/2) and the phase 3 study limited its ability to rely on the phase 1/2 study to support durability of effect.

“Gene therapy is in our communities’ future,” said the National Hemophilia Foundation’s President and CEO Dr. Leonard Valentino. “It must be brought to the community in a safe and effective form that provides a durable solution that is predictable for patients, clinicians, and payers.”

While this development shifts the timetable significantly by extending the BLA pending period, it does still present a path towards approval. To this end, the FDA recommends that the company actually complete the phase 3 study and submit two-year follow-up safety and efficacy data on all study participants. Full enrollment for the phase 3 study was achieved in November 2019, with two-year follows ups on all patients to be completed in November 2021.

“We remain committed to the hemophilia community and to leading the way to the first ever gene therapy in hemophilia A,” said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. “We are surprised and disappointed that the FDA introduced new expectations for the first time in the Complete Response Letter. We are confident in valoctocogene roxaparvovec gene therapy and its potential to redefine the treatment paradigm for people with hemophilia A.”

BioMarin plans to meet with the FDA in the coming weeks to align on the next steps to obtain approval.

Source: BioMarin press release dated August 19, 2020

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