RARE Daily

BioMarin Updates Data from Ongoing Phase 1/2 Study of Experimental Hemophilia A Gene Therapy

June 1, 2020

Rare Daily Staff

BioMarin Pharmaceutical updated its previously reported results of an open-label phase 1/2 study of valoctocogene roxaparvovec, its experimental gene therapy treatment for adults with severe hemophilia A saying all study participants remain off prophylactic therapy after a single dose.

Though factor VIII activity levels declined with the most recent years’ observations, the company said they remain in a range to prevent spontaneous bleeding events.

The data have been submitted as a late-breaking abstract to the World Federation of Hemophilia Virtual Summit to be held June 14 to 19.

People living with hemophilia A lack sufficient functioning factor VIII protein to help their blood clot and are at risk for painful and/or potentially life-threatening bleeds from even modest injuries. People with the most severe form of hemophilia A, who make up approximately half of the hemophilia A population, often experience painful, spontaneous bleeds into their muscles or joints. Individuals with the most severe form of hemophilia A. The standard of care for individuals with severe hemophilia A is a prophylactic regimen of replacement factor VIII infusions administered intravenously up to two to three times per week or 100 to 150 infusions per year.  Despite these regimens, many people continue to experience breakthrough bleeds, resulting in progressive and debilitating joint damage, which can have a major impact on their quality of life.

Valoctocogene roxaparvovec is an AAV-factor VIII gene therapy designed to restore adequate levels of factor VIII for normal clotting. The therapy is being developed as a one-time treatment for adults with severe hemophilia A and could eliminate the need for ongoing factor VIII treatments.

The updated results show cumulative mean annualized bleed rates (ABR) remain less than one in both of two dosing cohorts and below pre-treatment baseline levels. The mean ABR in year four for the 6e13 vg/kg cohort was 1.3, and the mean ABR in year three for the 4e13 vg/kg cohort was 0.5.

Over the past year, six of the seven participants in the 6e13 vg/kg cohort and five of the six participants in the 4e13 vg/kg cohort remain free of spontaneous bleeds. Factor VIII activity levels declined commensurate with the most recent years’ observations and remain in a range to prevent spontaneous bleeding events.  

“This additional data is an important step toward a potential first treatment of its kind for this devastating disease,” said John Pasi, professor at Barts and the London School of Medicine and Dentistry and chief investigator for the valoctocogene roxaparvovec phase 1/2 study, and a principal investigator for the phase 3 study. “Each year of data increases our knowledge of safety and efficacy and contributes to the growing body of scientific data on gene therapies in general and hemophilia A in particular.”

Overall, the safety profile of valoctocogene roxaparvovec remains consistent with previously reported data with no delayed-onset treatment related events. No participants developed inhibitors to factor VIII, and no participants withdrew from the study. No participants have developed thrombotic events.  The most common adverse events associated with valoctocogene roxaparvovec occurred early and included transient infusion-associated reactions and transient, asymptomatic, and mild to moderate rise in the levels of certain proteins and enzymes measured in liver function tests with no long-lasting clinical sequelae.

The U.S. Food and Drug Administration is reviewing the biologics license application for valoctocogene roxaparvovec under Priority Review with a decision expected by August 21, 2020. The FDA also granted valoctocogene roxaparvovec Breakthrough Therapy designation.

The European Medicines Agency validated the company’s Marketing Authorization Application for valoctocogene roxaparvovec, which has been in review under accelerated assessment since January. Recognizing valoctocogene roxaparvovec for its potential to benefit patients with unmet medical needs, the EMA granted access to its Priority Medicines (PRIME) regulatory initiative.  The company expects the review procedure to be extended by at least three months due to COVID-19 delays. The company also believes there is a high possibility that the MAA will revert to the standard review procedure, as is the case with most filings that initially receive accelerated assessment. Because of the combination of these events, BioMarin said it expects an opinion from the Committee for Medicinal Products for Human Use in late 2020 or early 2021.

“In just over four years since starting clinical trials in patients, we’ve submitted applications for marketing authorizations globally, and we continue to contribute to the growing body of scientific data in gene therapy for hemophilia A with five studies underway,” said Hank Fuchs, president of Worldwide Research and Development at BioMarin. “We continue to move forward with health authorities to make this treatment available for people with severe hemophilia A.”


Photo: Hank Fuchs, president of Worldwide Research and Development at BioMarin


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