Data from longest and largest hemophilia gene therapy study demonstrates sustained factor VIII expression and bleed control, with 81.3% of individuals remaining off prophylaxis
No new safety signals observed
BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced new data underscoring the long-term efficacy and safety of ROCTAVIAN® (valoctocogene roxaparvovec-rvox) were presented at the 33rd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Washington, D.C., June 21-25, 2025.
The Phase 3 GENEr8-1 trial demonstrated that durable bleed control and sustained factor VIII (FVIII) expression were maintained five years after treatment with ROCTAVIAN. FVIII activity remained consistent with previously reported results, and no new safety signals were observed. Across the entire trial, no participants developed FVIII inhibitors or experienced thromboembolic events, and there were no treatment-related malignancies across the five years of the study.
“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, M.D., director of the University of California San Francisco’s program for noncancerous blood disorders and Adult Hemophilia Treatment Center. “These results highlight the role that gene therapy may play in addressing the burdens of chronic disease management in people living with hemophilia A, while maintaining excellent bleed control.”
Among the 134 individuals who received ROCTAVIAN in the study, the rollover population of 112 patients from the 270-902 noninterventional lead-in study had baseline annualized bleeding rate (ABR) data prospectively collected during a period of at least six months while on routine FVIII prophylaxis prior to receiving ROCTAVIAN, and two of the 112 patients discontinued the study prior to year five.
After five years, FVIII activity was nearly stable compared to year four, with mean FVIII activity in the mild hemophilia range (one-stage assay = 24.0 IU/dL; chromogenic assay = 13.7 IU/dL); 73.5% of participants had FVIII levels in the mild hemophilia to normal range. The mean ABR for treated bleeds for the rollover population was 0.6 bleeds/year after year five. During year five, 77.8% of the remaining participants (n=108) in the rollover population had zero treated bleeds. At the end of year five, 81.3% (n=109) of participants remained off prophylaxis. Additionally, clinically relevant changes in health-related quality of life measures were observed over five years.
“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.”
Additional data presented at the meeting described a framework for the measurement of the “hemophilia-free mind” in people who have received a ROCTAVIAN infusion, which represents an easing of the physical and psychological burden of hemophilia. Researchers leveraged clinical data as well as questionnaires to assess a number of quality of life outcomes from baseline to week 104. The analysis showed that people who received ROCTAVIAN in the Phase 3 GENEr8-1 study experienced improvements across all measures, including bleeding risk, joint pain, injection schedule, physical activity, travel, employment and education, and impact on family members and caregivers.
“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,” said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. “We remain committed to supporting the medical community and individuals living with severe hemophilia A in the clinical adoption of this gene therapy so they can experience the benefits that this treatment can offer.”
Below are key presentations for BioMarin and ROCTAVIAN at ISTH (all times Eastern Daylight Time):
Efficacy, Safety and Quality of Life 5 Years After Valoctocogene Roxaparvovec Gene Transfer
Poster PB0804
Monday, June 23, 2025, 1:45 – 2:45 p.m.
Final Analysis of the Phase 1/2 Trial of Valoctocogene Roxaparvovec for Severe Hemophilia A
Poster PB0822
Monday, June 23, 2025, 1:45 – 2:45 p.m.
Impact of Valoctocogene Roxaparvovec on Hemophilia-Free Mind: A Visual Multidimensional Method
Poster PB0838
Monday, June 23, 2025, 1:45 – 2:45 p.m.
Mechanisms of AAV Vector Persistence Following Infant Gene Therapy in Severe Hemophilia A Dogs
Oral OC 51.1
Tuesday, June 24, 2025, 9:30 – 9:45 a.m.
Steady Musculoskeletal Health After Gene Therapy in Severe Hemophilia A: 5-Year Results
Oral OC 69.1
Wednesday, June 25, 2025, 10:15 – 10:30 a.m.
