Roctavian Demonstrates Sustained Efficacy and Safety in Patients With Hemophilia A

BioMarin Pharmaceutical Inc has released 5-year follow-up data from its pivotal phase 3 GENEr8-1 trial of Roctavian (valoctocogene roxaparvovec-rvox), highlighting the gene therapy’s enduring efficacy and favorable safety profile in adults with severe hemophilia A. These findings were presented during the 33rd Congress of the International Society on Thrombosis and Haemostasis (ISTH), held June 21-25 in Washington, DC.

The trial data underscore Roctavian’s long-term potential as a transformative treatment option. After 5 years of follow-up, participants continued to experience clinically meaningful bleed control with sustained factor VIII (FVIII) activity. Mean FVIII levels remained in the mild hemophilia range (24.0 IU/dL via one-stage assay; 13.7 IU/dL via chromogenic assay), with 73.5% of patients maintaining FVIII activity in the mild to normal range.

Among the 112 patients in the rollover population who had at least 6 months of baseline data from routine FVIII prophylaxis, only two discontinued the study before year 5. The mean annualized bleeding rate (ABR) for treated bleeds was 0.6 bleeds/year in year 5. Notably, 77.8% of patients had zero treated bleeds during that time. At year 5, 81.3% remained off prophylaxis, emphasizing the durability of response. No participants developed FVIII inhibitors or experienced thromboembolic events, and no treatment-related malignancies were reported over the full 5 years.

The durability of bleed control and discontinuation of prophylaxis in over 80% of participants support potential reductions in the cumulative cost of FVIII replacement therapies, which remain a significant burden in chronic care. The trial’s long-term data also reinforce the stability of Roctavian’s safety profile—a key consideration for coverage and formulary decisions in the gene therapy landscape.

Andrew Leavitt, MD, director of the Adult Hemophilia Treatment Center at University of California, San Francisco remarked, “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.”

Patient-reported outcomes and health-related quality of life (HRQoL) metrics also reflected significant improvements. A newly introduced framework for assessing the "hemophilia-free mind" evaluated both physical and psychological dimensions post-treatment. Using clinical metrics and questionnaires, improvements were noted in joint pain, injection frequency, mobility, travel, education, employment, and family impact.

BioMarin reaffirmed its dedication to advancing access and adoption of gene therapy in hemophilia A. “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, MD, Executive Vice President and Chief Research & Development Officer at BioMarin.

Overall, the therapy demonstrates durable efficacy, with sustained bleed control and minimal need for prophylaxis over 5 years. Its safety profile remains consistent, with no new safety signals, no development of FVIII inhibitors, and no treatment-related malignancies reported throughout the study period. Importantly, Roctavian offers the potential for long-term cost offsets due to the reduced reliance on FVIII replacement therapy. Additionally, clinically meaningful improvements in both physical and mental health-related quality of life metrics were observed, underscoring the broader impact of gene therapy beyond clinical outcomes.

Reference

BioMarin presents five-year phase 3 results reinforcing long-term efficacy and safety of Roctavian® (valoctocogene roxaparvovec-rvox) at International Society on Thrombosis and Haemostasis 2025 Congress. News release. BioMarin. June 24, 2025. Accessed August 1, 2025. https://www.biomarin.com/news/press-releases/biomarin-presents-five-year-phase-3-results-reinforcing-long-term-efficacy-and-safety-of-roctavian-valoctocogene-roxaparvovec-rvox-at-international-society-on-thrombosis-and-haemostasis-2025-c/