FDA approves BioMarin gene therapy for hemophilia A


BioMarin Pharmaceutical Inc. 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 (congenital factor VIII (FVIII) deficiency with FVIII activity < 1 IU/dL) without antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test.

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

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

“The approval of ROCTAVIAN, as the first gene therapy for severe hemophilia A, has the potential to transform the way we treat adults based on years of bleed control following a single, one-time infusion.”

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

With the current standard of care, individuals undergo lifelong preventative therapy, receiving infusions or injections at burdensome routine intervals to maintain enough clotting factor in the bloodstream to prevent bleeds. ROCTAVIAN is designed to replace the function of the mutated gene, allowing people with severe hemophilia A to produce their own FVIII and thereby limit bleeding episodes.

“Today’s approval of ROCTAVIAN builds on BioMarin’s proven track record of advancing treatments that target the underlying cause of life-threatening genetic conditions, which has produced eight best- or first-in-class commercial therapies,” said Jean-Jacques Bienaimé, chairman and chief executive officer of BioMarin. 

“We are proud to now offer adults with severe hemophilia A, a one-time, single-dose treatment option. We are especially grateful to the bleeding disorders community for its support of this program, and to all the patients and healthcare providers who participated in our clinical trials.”

ROCTAVIAN is manufactured at the company’s facility in Novato, California. The BioMarin-owned 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 hemophilia study

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

As reported in the FDA-approved labeling for ROCTAVIAN, the 112 patients in whom 6-month baseline ABR was collected prospectively experienced a mean ABR reduction of 52% after receiving ROCTAVIAN (2.6 bleeds/year) through end of follow-up (median of three years) compared to their baseline ABR while receiving routine FVIII prophylaxis (5.4 bleeds/year).  

This result was based on an FDA analysis that imputed an ABR of 35 in 13 patients for the periods when these patients were on prophylaxis. These patients also reported a substantial reduction in the rate of spontaneous bleeds and joint bleeds following treatment with ROCTAVIAN (observed mean ABR of 0.5 bleeds/year for spontaneous bleeds and 0.6 bleeds/year for joint bleeds) compared to their baseline rate while receiving routine FVIII prophylaxis (observed mean ABR of 2.3 bleeds/year for spontaneous bleeds and 3.1 bleeds/year for joint bleeds).

The majority of study participants continued to respond to treatment through year three and beyond, without supplemental use of regular prophylaxis.

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

Data presented 

Additionally, results from the three-year analysis of the Phase 3 GENEr8-1 study that were presented at ISTH showed that study participants had an 82.9% reduction in treated bleeds overall compared with baseline. The study also found ROCTAVIAN led to a 96.8% reduction in FVIII usage overall compared with baseline.

BioMarin will begin educating physicians and patients about ROCTAVIAN immediately to ensure the hemophilia community is aware of this new treatment option.

As part of the development of ROCTAVIAN, BioMarin has worked with private and public payers in the U.S. in parallel to enable access, with the goal of ensuring that every eligible adult interested in ROCTAVIAN is able to receive treatment.

BioMarin’s approach

A key component of the company’s approach to access is the outcomes-based warranty, which will be offered to all U.S. insurers. The warranty will reimburse government and commercial payers up to 100% of wholesale acquisition cost in the event that a person does not respond to ROCTAVIAN. If an individual treated with ROCTAVIAN loses response at any time in the first four years after dosing, BioMarin will reimburse payers on a prorated basis for the cost of treatment.

Most people with hemophilia receive care at HTCs. The company is working with U.S. HTCs to ensure that the centers are prepared to administer ROCTAVIAN following today’s approval. 

“Our teams have been working for many months to ensure that the people who are eligible for ROCTAVIAN have access to this first-in-class medicine,” said Jeff Ajer, executive vice president and chief commercial officer of BioMarin.

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

It is estimated that there are approximately 6,500 adults living with severe hemophilia A in the U.S. BioMarin expects approximately 2,500 of those adults to be eligible to receive ROCTAVIAN with this initial approval.

Newsletter Signup - Under Article / In Page

"*" indicates required fields

Subscribe to our newsletter to get the latest biotech news!

This field is for validation purposes and should be left unchanged.

Suggested Articles

Show More