Val-rox Meets End Points in Hemophilia A at 3 Years


The new analysis data was requested by the FDA ahead of the therapy’s March 31, 2023 PDUFA date.

A 3-year analysis of the phase 3 GENEr8-1 study (NCT03370913) has revealed that the study’s primary and secondary endpoints have continued to be met and valoctocogene roxaparvovec (val-rox; Roctavian; BioMarin) has a durable effect on annualized bleeding rate (ABR) and factor VIII (FVIII) usage in patients with hemophilia A.1

"We continue to learn more about the durability, safety and efficacy of val-rox," investigator Steven Pipe, MD, Professor of Pediatrics and Pathology, University of Michigan, said in a statement.1 "I am encouraged to see the consistent clinical response and the significant number of study participants who remain off prophylaxis after 3 years. This shows the potential transformative impact of this single treatment event for people with severe hemophilia A."

The new analyses found that mean FVIII activity was 18.8 IU/dL (median, 8.4) in year and 15.2 IU/dL (median, 7.4) in year 4; mean ABR was 1.9 (median, 0.0) in year 3 and 0.8 (median, 0.0) in year 4; and mean annualized FVIII utilization was 8.4 infusions per year (median, 0.0) in year 3 and 11.1 in year 4 (median, 0.0). These measurements compared to baseline all have P values of less than .001. At the end of Year 3, 92% of patients remained off prophylaxis and those who returned to FVIII or emicizumab prophylaxis did so safely.

WATCH NOW: Steven Pipe, MD, on Continuing Durability of Hemgenix in Hemophilia B

"The 3-year data reinforce our belief that Roctavian has the potential to fundamentally transform the treatment of severe hemophilia A for patients and eliminate the burden of prophylaxis," Hank Fuchs, MD, President of Worldwide Research and Development, BioMarin, added to the statement.1 "We look forward to sharing these data with the FDA as part of our ongoing regulatory review. We remain grateful to the bleeding disorders community for its support of our robust clinical program."

BioMarin announced in November 2022 that the biologics license application (BLA) review for val-rox that the FDA will no longer be holding an advisory committee meeting to discuss the therapy’s benefit. The current PDUFA date is March 31, 2023.2 Earlier in November, BioMarin had disclosed that the PDUFA target action date may be delayed if the FDA deems the submission of new data from the analyses as a major amendment to the application.3 BioMarin’s resubmited BLA was accepted by the FDA in October 2022, following marketing authorization by the European Commission in August 2022. Val-rox has received RMAT, breakthrough therapy, and orphan drug designations from the FDA.

"The review of a BLA is a dynamic process, and we appreciate FDA's ongoing engagement as we work toward delivering a potentially transformative treatment choice to those patients with severe hemophilia A," Hank Fuchs, MD, President, Worldwide Research and Development, BioMarin, said in a statement."We look forward to further dialogue with the Agency as it reviews our application."

1. Biomarin Announces Stable and Durable Annualized Bleed Control for ROCTAVIAN™ in largest phase 3 gene therapy study in adults with severe hemophilia A; 134-participant study met all primary and secondary efficacy endpoints at 3-year analysis. News release. Biomarin. January 8, 2023.
2. BioMarin announces advancements in FDA review of ROCTAVIAN™ (valoctocogeneroxaparvovec) for adults with severe hemophilia A. News release. BioMarin Pharmaceuticals. November 23, 2022.
3. BioMarin Announces Incremental Progress on Biologics License Application (BLA) Review for Valoctocogene Roxaparvovec AAV Gene Therapy for Adults with Severe Hemophilia A Program. News release. BioMarin Pharmaceutical. November 7, 2022.
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