Roctavian Gene Therapy Controls Bleeding for Five Years in Severe Hemophilia A

New five-year results from the phase 3 GENEr8-1 trial show that BioMarin’s gene therapy Roctavian (valoctocogene roxaparvovec-rvox) continues to provide long-term control of bleeding and sustained factor VIII (FVIII) expression, with more than 80% of participants remaining off routine prophylaxis.

Roctavian is a gene therapy designed to treat adults with severe hemophilia A, a genetic disorder caused by a deficiency of FVIII, a protein necessary for blood clotting. Without enough FVIII, people with hemophilia A experience frequent bleeding episodes, often requiring regular intravenous infusions of the missing clotting factor to prevent life-threatening bleeds and joint damage.

The therapy uses an adeno-associated virus (AAV5) vector to deliver a working copy of the FVIII gene to liver cells, enabling the body to produce its own clotting factor. This approach offers the potential for a long-lasting effect from a single infusion, reducing or eliminating the need for ongoing preventive (prophylactic) treatments.

A single dose of Roctavian maintained FVIII levels at near-normal or normal levels for most participants, significantly reducing the need for regular FVIII infusions.

In June, BioMarin presented the five-year data at the 33rd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Washington, D.C. The GENEr8-1 trial is the largest and longest-running clinical study of a gene therapy in hemophilia A. It included 134 participants, most who had been previously enrolled in a lead-in study where their baseline bleeding rates were measured while on standard FVIII prophylaxis.

Five years after receiving Roctavian, participants continued to experience reduced bleeding and stable FVIII levels. FVIII activity remained in the mild hemophilia range, with average levels of 24.0 IU/dL by one-stage assay and 13.7 IU/dL by chromogenic assay. In addition, 73.5% of participants had FVIII levels in the mild to normal range.

A single dose of Roctavian maintained FVIII levels at near-normal or normal levels for most participants, significantly reducing the need for regular FVIII infusions. The data reinforce the therapy’s ability to lessen the daily burden of living with hemophilia A and improve patients’ overall quality of life.

The mean annualized bleeding rate (ABR) for treated bleeds in the rollover population was 0.6 bleeds per year at year five. Most participants (77.8%) had no treated bleeds during that fifth year. At the same time, 81.3% of participants remained off routine prophylaxis.

Safety outcomes were also positive.

Over the five years of follow-up, there were no new safety signals, no development of FVIII inhibitors (antibodies that block the therapy’s effect), and no treatment-related malignancies or thromboembolic events.

Beyond the clinical results, the study also tracked improvements in quality of life. Participants reported better outcomes across several measures, including reduced joint pain, fewer limitations on physical activity and travel, and reduced impact on work, education, and family life.

“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,” Dawn Rotellini, chief operating officer at the National Bleeding Disorders Foundation, said in a news release. “It is meaningful for the bleeding disorders community to see a continued commitment to highlighting the benefits of hemophilia A gene therapy.”

Researchers also introduced the concept of a “hemophilia-free mind”—a shift in how people with hemophilia perceive their disease. Using clinical data and patient questionnaires, they evaluated changes in psychological and emotional well-being over time. The report showed improvements across all categories, reflecting a reduced daily burden of the disease.

Hemophilia A affects about 1 in 10,000 people and is usually inherited, although about one-third of cases are caused by spontaneous mutations. Roctavian is approved for use in adults with severe hemophilia A who do not have antibodies to the AAV5 vector used in the therapy.