FDA Approves $2.9 Million Gene Therapy for Hemophilia A

The FDA has approved BioMarin Pharmaceutical’s Roctavian (valoctocogene roxaparvovec-rvox) to treat adults with severe hemophilia A. The one-time, single-dose infusion is the first approved gene therapy for severe hemophilia A. Hemophilia A is a genetic disease caused by the deficiency of clotting factor VIII. It is the most common type of hemophilia and occurs much more frequently in males; incidence is estimated at 1 in 4,000-5,000 male births.

Roctavian is designed to replace the function of the mutated gene, allowing people with severe hemophilia A to produce their own Factor VIII and thereby limit bleeding episodes. The gene therapy uses an adeno-associated virus vector to deliver a functional gene to the cells in the liver, allowing the body to produce its own Factor VIII.

Roctavian, which will available in about eight weeks, will have a wholesale acquisition cost of $2.9 million based on the weight of a typical patient, the company said in an investor call. The company indicated that Roctavian adds value in terms of both the clinical benefit it offers patients and the economic benefit, which is about $800,000 a year for the typical patient.

BioMarin is offering an outcomes-based warranty that 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 Rocktavian 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.

“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,” Steven Pipe, M.D., professor of pediatrics and pathology at the University of Michigan and an investigator in the phase 3 study, said in a press release.

The FDA approval is based on data from the global phase 3 GENEr8-1 study. The 112 patients who received Roctavian experienced a mean annualized bleeding rate reduction of 52% compared with those receiving routine Factor VIII prophylaxis. 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 postapproval studies to follow those dosed in a real-world setting for 15 years.

In the clinical trials, Roctavian was well-tolerated. The prescribing information includes warnings and precautions for infusion-related reactions, hepatotoxicity, thromboembolic events and theoretical risk of hepatocellular carcinoma.

Gene therapies for hemophilia have been a focus of research efforts. In November 2022, the FDA approved CSL Behring’s Hemgenix (etranacogene dezaparvovec) to treat adults with hemophilia B who currently use factor IX prophylaxis therapy. With a cost of $3.5 million, Hemgenix is an adeno-associated virus vector-based gene therapy and is a one-time product given as a single dose by IV infusion. The therapy uses an adeno-associated virus as a vector that carries the Padua gene variant of Factor IX, which generates factor IX proteins. The gene is expressed in the liver to produce factor IX protein to increase blood levels of factor IX to limit bleeding episodes.

Related: FDA Approves $3.5 million Gene Therapy Hemgenix for Hemophilia B

Additionally, the FDA is currently reviewing Pfizer’s biologics license application (BLA) for fidanacogene elaparvovec to treat adults with hemophilia B; the agency has assigned an action date in the second quarter of 2024. Fidanacogene elaparvovec is a one-time gene therapy that contains a bio-engineered adeno-associated virus capsid and a high-activity variant of the Factor IX gene. Pfizer licensed the gene therapy from Spark Therapeutics.

The Institute for Clinical and Economic Review in December 2022 issued a final evidence report for both Hemgenix and Roctavian. ICER found that both treatments would lead to cost savings and projected gains in quality adjusted life years. For Hemgenix, ICER had used its price of $3.5 million and a placeholder price of $2.5 million for Roctavian. ICER reviewers said the savings come from the offsetting the price of prophylaxis with existing agents that cost in excess of $300,000 per year.