FDA Approves BioMarin’s Roctavian Gene Therapy for Adults with Severe Hemophilia A

Rare Daily Staff

The U.S. Food and Drug Administration approved BioMarin Pharmaceutical’s Roctavian gene therapy for the treatment of adults with severe hemophilia A deficiency.

The approval was for the treatment of adults with severe hemophilia A deficiency with FVIII activity less than 1 IU/dL without antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.

The one-time, single-dose infusion is the first approved gene therapy for severe hemophilia A in the United States. The approval comes almost three years after an initial FDA rejection in 2020 and a recent delay of the review. 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.

“We are proud to now offer adults with severe hemophilia A, a one-time, single-dose treatment option,” said Jean-Jacques Bienaimé, chairman and CEO of BioMarin. “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.”

The FDA approval is based on data from the global pPhase 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 3 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 percent 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. Safety results for 134 patients through three years demonstrated that Roctavian was well-tolerated.

BioMarin said it 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.

Additionally, results from the three-year analysis of the phase 3 GENEr8-1 study that were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2023 Congress that showed that study participants had an 82.9 percent reduction in treated bleeds overall compared with baseline. The study also found Roctavian led to a 96.8 percent reduction in FVIII usage overall compared with baseline.

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.

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

During a conference call following approval, BioMarin said it will price Roctavian at a wholesale acquisition cost of $2.9 million. BioMarin said it 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. 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 percent of wholesale acquisition cost in the event that a person does not respond to the gene therapy. 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.

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.

Photo: Jean-Jacques Bienaimé, chairman and CEO of BioMarin