BioMarin Pharmaceuticals Hemophilia A Data Indicate Potential for "Sustained Bleed Control"

The results of BioMarin Pharmaceuticals valoctocogene roxaparvovec gene therapy are positive. (Courtesy of Michael Vi/Getty Images)

The results of BioMarin Pharmaceuticals' valoctocogene roxaparvovec gene therapy are positive. (Courtesy of Michael Vi/Getty Images)

BioMarin Pharmaceuticals has published results in the New England Journal of Medicine from its Phase III clinical trial of valoctocogene roxaparvovec. The investigational gene therapy is intended for the treatment of adults with severe hemophilia A. 

Hemophilia A is an X-linked genetic disorder caused by insufficient levels of Factor VIII, a blood protein responsible for proper clotting. Because of this deficiency, people with hemophilia A have difficulty stopping the flow of blood from wounds.  

Those with the condition are prone to prolonged bleeding episodes after surgeries, dental procedures, injury or trauma, and can experience bruising and bleeding of the mucous membranes. Hemophilia A is considered to be severe when there is less than 1% of normal Factor VIII clotting activity, and it is associated with spontaneous bleeding, which can occur in any organ system.  

Currently, patients with hemophilia A are treated with prophylactic infusions of replacement factor VIII administered intravenously, sometimes two to three times per week, accumulating to 100 to 150 infusions per year. BioMarin Pharmaceuticals is looking to change the treatment landscape with its single-dose genetic therapy. 

The results of BioMarin Pharmaceuticals Therapy for Hemophilia A

In the published results, BioMarin Pharmaceuticals shared that after a single infusion of valoctocogene roxaparvovec, patients experienced substantially reduced annualized bleeding rates, reduced Factor VIII utilization and increased Factor VIII activity. Additionally, 90% of patients dosed had either no treated bleeds or fewer treated bleeds after infusion as compared to Factor VIII prophylactic treatment. At weeks 49 and 52 following treatment, 88% of participants had a median Factor VIII activity of 5 IU/dL or higher, a change that is associated with lessened severity of the disease. 

"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, Ph.D., director of Hemocentro UNICAMP, University of Campinas and lead principal investigator of the GENEr8-1 study. "These results reflect the potential for sustained hemostatic bleed control with this gene therapy for hemophilia A." 

Valoctocogene roxaparvovec has been studied longer than any other gene therapy for hemophilia A, according to BioMarin Pharmaceuticals. The therapeutic has a favorable tolerability and safety profile with no participants developing inhibitors to Factor VIII, malignancy or thromboembolic events. Common adverse events associated with the therapeutic included headache, arthralgia and nausea, as well as a moderate rise in liver enzymes, which was not associated with any long-lasting clinical events. 

Potential benefits of BioMarin’s valoctocogene roxaparvovec include zero bleeds for patients, avoiding the use of prophylactic therapy and providing a one-time treatment to control the disease. BioMarin Pharmaceuticals has other clinical studies underway in its comprehensive gene therapy program for the treatment of hemophilia A, including a dose-escalation study of valoctocogene roxaparvovec. This study involves dosing participants who have pre-existing AAV5 antibodies, which demonstrate immunity against gene therapy and evaluating the therapeutic in patients with active or prior Factor VIII inhibitors.  

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