FDA approves BioMarin gene therapy for hemophilia A


has announced that the United States Food and Drug Administration (FDA) has approved ROCTAVIAN (valoctocogene roxaparvovec-rvox) gene therapy for the treatment of adults with severe hemophilia A (inherited factor VIII deficiency (FVIII) with FVIII activity < 1 IU/dL) without antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test.

A one-time single-dose infusion is the first gene therapy approved for severe hemophilia A in the US. ROCTAVIAN was first approved by the European Medicines Agency in August 2022.

“Adults with severe hemophilia A face a lifetime burden, with frequent infusions and a high risk of health complications, including uncontrolled bleeding and irreparable joint damage,” said Steven Pipe, professor of pediatrics and pathology at the University of Michigan and a researcher at the University of Michigan. Phase 3 study.

“The approval of ROCTAVIAN, as the first gene therapy for severe hemophilia A, has the potential to change the way we treat adults based on bleeding control for years after a single infusion.”

Hemophilia A is a lifelong genetic condition caused by mutations in the gene responsible for producing a protein called FVIII, which is necessary for blood clotting. When the amount is severely deficient, the condition puts people with hemophilia A at risk for painful and potentially life-threatening bleeding, which can occur spontaneously.

By current standards of care, individuals are on lifelong preventive therapy, receiving infusions or injections at routinely aggravating intervals to maintain sufficient clotting factors in the bloodstream to prevent bleeding. ROCTAVIAN was designed to override the function of the mutated gene, allowing people with severe hemophilia A to produce their own FVIII and thereby limiting bleeding episodes.

“Today’s approval of ROCTAVIAN builds on BioMarin’s proven track record in advanced treatments targeting underlying causes of life-threatening genetic conditions, which have resulted in eight best or first-in-class commercial therapies,” said Jean-Jacques Bienaimé, chairman and principal BioMarin executive.

“We are proud to now offer adults with severe hemophilia A a single-dose one-time treatment option. We are very grateful to the bleeding disorders community for supporting this program, and to all patients and healthcare providers participating in our clinical trial.”

ROCTAVIAN is manufactured at the company’s facility in Novato, California. BioMarin’s site is one of the largest gene therapy manufacturing facilities of its kind and will allow the company to meet commercial demand throughout its product lifecycle.

Largest phase 3 gene therapy study of hemophilia

FDA approval is based on data from the global phase 3 study GENEr8-1, the largest phase 3 trial of any gene therapy in hemophilia. Of the 134 patients who received ROCTAVIAN in this study, 112 patients had baseline annualized bleeding rate (ABR) data collected prospectively over a period of at least 6 months on FVIII prophylaxis prior to receiving ROCTAVIAN. The remaining 22 patients had baseline ABR retrospectively pooled. All patients were followed for at least three years.

As reported in the FDA-approved labeling for ROCTAVIAN, 112 patients whose initial 6-month ABR were prospectively pooled experienced a median ABR reduction of 52% after receiving ROCTAVIAN (2.6 bleeding/year) to the end of follow-up (median of three years) compared to their initial ABR while receiving routine FVIII prophylaxis (5.4 bleeding/year).

These results are based on an FDA analysis that calculated ABR 35 in 13 patients during the period when these patients were taking prophylaxis. These patients also reported a substantial reduction in the rate of spontaneous bleeding and joint bleeding after treatment with ROCTAVIAN (mean ABR observed of 0.5 bleeding/year for spontaneous bleeding and 0.6 bleeding/year for joint bleeding) compared with their baseline level while receiving routine prophylactic FVIII (observed a mean ABR of 2.3 bleeding/year for spontaneous bleeding and 3.1 bleeding/year for joint bleeding).

The majority of study participants continued to respond to treatment for three years and beyond, without the additional use of regular prophylaxis.

BioMarin will continue to monitor long-term treatment effects with extension studies that will follow all clinical trial participants for up to 15 years, as well as post-approval studies to follow those dosed in real-world settings for 15 years or more.

Data presented

In addition, results from a three-year analysis of the GENEr8-1 Phase 3 study presented at ISTH showed that study participants experienced an 82.9% reduction in bleeding treated overall compared to baseline. The study also found that ROCTAVIAN led to a 96.8% decrease in FVIII use overall compared to baseline.

BioMarin will soon start educating doctors and patients about ROCTAVIAN to ensure the hemophilia community is aware of this new treatment option.

As part of the development of ROCTAVIAN, BioMarin has been working with private and public payers in the US in parallel to enable access, with the goal of ensuring that any eligible adult interested in ROCTAVIAN can receive treatment.

The BioMarin Approach

A key component of the company’s approach to access will be results-based guarantees, which will be offered to all US insurers. The guarantee will reimburse government and commercial payers for up to 100% of wholesale acquisition costs if someone does not respond to ROCTAVIAN. If a person being treated with ROCTAVIAN loses response at any time within the first four years after dosing, BioMarin will reimburse the payer on a pro-rated basis for the cost of treatment.

Most people with hemophilia receive treatment at HTCs. The company is working with HTC US to ensure that the center is ready to administer ROCTAVIAN following today’s approval.

“Our team has been working for months to ensure that people who qualify for ROCTAVIAN have access to this class of drug,” said Jeff Ajer, executive vice president and commercial director of BioMarin.

“We value our close partnership with health insurance, hemophilia treatment centers and the hemophilia community to ensure the greatest access for people with severe hemophilia A.”

It is estimated that there are about 6,500 adults living with severe hemophilia A in the US. BioMarin expects approximately 2,500 of these adults to be eligible to receive ROCTAVIAN with this pre-approval.


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