Roctavian sustains bleed control, maintains factor VIII for 5 years
Patients gain 'hemophilia-free mind' with reduced bleeds
A single dose of Roctavian (valoctocogene roxaparvovec-rvox), a gene therapy for severe hemophilia A from BioMarin Pharmaceutical, maintains factor VIII (FVIII) levels at near-normal or normal levels for up to five years, with most patients staying off prophylaxis, or preventive treatment.
These lasting benefits were observed in GENEr8-1 (NCT03370913), a global Phase 3 clinical study. The study showed Roctavian reduced the need for regular FVIII infusions, and also reduced the daily burden of living with hemophilia A, leading to a better quality of life for patients.
“These five-year data reinforce our confidence in Roctavian’s profile, showing that people living with severe hemophilia A can experience long-term bleed control without the need for prophylaxis, meaningfully impacting the mental and clinical burdens of this condition,” Greg Friberg, MD, BioMarin’s executive vice president and chief research and development officer, said in a company press release.
The data, which update an earlier four-year readout of how safe Roctavian is and how well it works in the long term, were presented in three posters at the International Society on Thrombosis and Haemostasis 2025 congress, held June 21-25 in Washington.
Hemophilia A is a genetic disease in which the body doesn’t produce enough functional FVIII, a protein needed for blood to clot properly. Without FVIII, even minor injuries can cause excessive bleeding. Maintaining FVIII levels close to or within the normal range is important for preventing bleeds.
Gene therapy helps body make its own FVIII
Roctavian is designed to deliver the genetic instructions that enable cells in the liver to produce functional FVIII on their own. Its approval in the U.S. drew on positive data from the GENEr8-1 clinical study, which showed that most patients remained free of bleeds three years after receiving a single dose of the gene therapy.
Of the 134 men with severe hemophilia A who received Roctavian, 112 had participated in a lead-in study. In that study, their annualized bleeding rate — the average number of bleeding episodes per year — was recorded while they were on routine FVIII prophylaxis. This group of 112 patients formed the primary analysis population for FVIII use and bleeding rates. Two of them left the study before the five-year mark.
By year five, FVIII levels stayed close to those observed at year four, with most patients (73.5%) falling within the mild hemophilia or normal range.
The mean annualized bleeding rate among those who had previously been on standard FVIII prophylaxis dropped to 0.6 bleeds per year. Most patients (77.8%) having zero treated bleeds during year five, and the majority (81.3%) remained off prophylaxis at the end of year five.
None of the patients tested positive for FVIII inhibitors (neutralizing antibodies targeting FVIII that can make treatment less effective) or experienced blood clots or cancer.
There also were “no new safety signals,” researchers wrote in an abstract to the poster titled, “Efficacy, Safety and Quality of Life 5 Years After Valoctocogene Roxaparvovec Gene Transfer.”
“I am impressed that the strong efficacy and safety results for Roctavian are sustained five years after individuals with severe hemophilia A received gene therapy, with only one adult returning to prophylaxis since the last data cut,” said Andrew Leavitt, MD, a professor at the University of California San Francisco, who presented the poster at the congress.
Roctavian also improved patients’ health-related quality of life. In another poster, researchers described a framework for measuring what they call a “hemophilia-free mind” — a reduction of the disease’s daily burden. Over two years, patients saw improvements across all areas, with the greatest gains observed in reducing bleeds and the need for regular FVIII infusions.
The researchers also presented final data from a smaller Phase 1/2 clinical study (NCT02576795) in which Roctavian nearly zeroed out the number of bleeds and the need for prophylaxis in 13 men with severe hemophilia A, with the mean annualized bleeding rate dropping by up to 96% for as long as seven years.
Eight of the 12 patients who completed seven years in the study “remain off prophylaxis,” the researchers wrote in an abstract to the poster titled, “Final Analysis of the Phase 1/2 Trial of Valoctocogene Roxaparvovec for Severe Hemophilia A.”
“We hope these results demonstrating the long-term durability of gene therapy equip individuals with severe hemophilia A with the knowledge to make informed decisions regarding treatment,” said Dawn Rotellini, chief operating officer at the National Bleeding Disorders Foundation. “It is meaningful for the bleeding disorders community to see a continued commitment to highlighting the benefits of hemophilia A gene therapy.”
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