A single infusion of valoctocogene roxaparvovec gene therapy greatly increased factor VIII (FVIII) production and reduced the annualized bleeding rate and use of concentrated FVIII in patients with hemophilia A, according to a 1-year analysis of study data published in the New England Journal of Medicine.

The results showed that participants had increased mean FVIII levels by 41.9 IU/dL (95% CI, 34.1-49.7 IU/dL; median change 22.9 IU/dL) roughly 1 year after receiving their infusions (49-52 weeks).

After week 4, the higher production of FVIII led to a 98.6% reduction in the annualized rates of FVIII concentrate use among participants compared to the year prior to infusion (P <.001). The mean annualized rates of treated bleeding had also decreased by 83.8% after week 4 in the study (P <.001).

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“Breakthrough bleeding represents a high burden of disease management and an unmet medical need for many people. I am encouraged that during the first year of treatment, 90% of study participants had either zero treated bleeds or fewer treated bleeds post-infusion than with factor VIII prophylaxis,” said Margareth C. Ozelo, MD, PhD, lead principal investigator of the GENEr8-1 study.

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“These results reflect the potential for sustained hemostatic bleed control with this gene therapy for hemophilia A,” Dr. Ozelo added. A total of 134 adult patients with severe hemophilia A (FVIII ≤1 IU/dL) received 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight in the phase 3 GENEr8-1 study.

All participants had at least 1 adverse event with 16.4% reporting serious adverse events. The most frequent event was an elevation of alanine aminotransferase levels which occurred in 85.8% of patients and was managed with immunosuppressants.

Other adverse events included headache (38.1%), nausea (37.3%), and elevated aspartate aminotransferase levels (35.1%). No patients developed FVIII inhibitors nor experienced thrombosis during the study.

“Valoctocogene roxaparvovec has been studied longer than any other gene therapy for hemophilia A, and year after year, we continue to increase our knowledge of how this investigational therapy may potentially benefit the lives of people with hemophilia A,” said Hank Fuchs, MD, president of Worldwide Research and Development at BioMarin.


BioMarin announces publication in New England Journal of Medicine of one-year results from phase 3 pivotal trial with valoctogene roxaparvovec gene therapy in adults with severe hemophilia A. News release. BioMarin Pharmaceutical; March 17, 2022.

Ozelo MC, Mahlangu J, Pasi KJ, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386(11):1013-1025. doi:10.1056/NEJMoa2113708