BioMarin's hemophilia gene therapy Roctavian lands FDA nod with 'glimmers' of enthusiasm among doctors

After an initial rejection in 2020 and a review delay earlier this year, BioMarin’s Roctavian has finally got the FDA go-ahead to introduce a gene therapy for a not-so-rare disorder.

The FDA has cleared Roctavian as a one-time therapy for adults with severe hemophilia A, BioMarin said Thursday.

The news comes seven months after the FDA greenlighted CSL Behring’s hemophilia B gene therapy Hemgenix, which bears a list price of $3.5 million and is currently the most expensive drug in the world.

BioMarin is pricing Roctavian at a wholesale acquisition cost of $2.9 million, BioMarin’s chief commercial officer Jeff Ajer said during a call Thursday. It’s also setting up an outcomes-based warranty program. The warranty will reimburse government and commercial payers up to the full cost if Roctavian doesn’t live up to its treatment expectations. Partial reimbursement will be granted if an individual loses response to the therapy in the first four years after dosing.

In a recent health economics analysis, the drug pricing watchdog Institute for Clinical and Economic Review figured Roctavian would be cost effective at around $2 million per treatment under some commonly used standards.

Hemophilia A is more prevalent than hemophilia B, affecting about 1 in 10,000 people. But Roctavian is only allowed to treat those with severe disease.

BioMarin estimates that about 6,500 adults suffer from severe hemophilia A in the U.S. Besides, because Roctavian uses adeno-associated virus serotype 5 (AAV5) to deliver a functional gene to produce factor VIII, only patients who test negative for AAV5-targeted antibody are eligible to receive the therapy. The company expects about 2,500 patients will be eligible to receive Roctavian.

Roctavian’s FDA-approved label now shows that 112 patients who got the gene therapy in the phase 3 GENEr8-1 trial experienced an average 52% reduction in bleeding cases per year through a median three years of follow-up. Most patients were still responding beyond three years without the need for regular prophylaxis, the company said.

The FDA reached the 52% number after removing certain events when patients also received FVIII prophylaxis, BioMarin said. The magnitude of improvement on yearly bleeding episodes is notably smaller than the 85.5% Roctavian has for its EU approval.

“The FDA is labeling the product with an intention to describe the sole contribution of Roctavian to bleeding outcomes independent of confounding effects such as factor use,” BioMarin’s R&D chief Henru Fuchs, M.D., said on Thursday’s call.

When asked whether the reduced efficacy data would affect payers’ view of Roctavian, Ajer pointed to a 96.8% reduction in FVIII usage compared with baseline, arguing “that’s going to be a key driver of people’s perception of the economic side of the value.”

With Roctavian, BioMarin faces a unique challenge. Unlike the more than a dozen gene therapies that the FDA has approved so far, Roctavian is meant for a disease that has plenty of other treatment options. For example, Roche’s antibody drug Hemlibra has gained vast traction with blockbuster sales. So Roctavian’s initial sales ramp will be slow, SVB Securities analysts said.

“However, we believe that BioMarin’s perseverance, time spent connecting with the medical community over a longer than anticipated time to market, and extended long-term data could ultimately help the launch,” the SVB team wrote in a note Tuesday.

The SVB team polled 18 U.S.-based doctors that treat hemophilia A. Most specialists are impressed with Roctavian’s efficacy and safety data, although their feedback suggests patients who are already on Hemlibra are less likely to switch.

Overall, the doctors suggested Roctavian could eventually capture about a quarter of all eligible severe hemophilia A patients at peak. The survey results reflect “glimmers” of enthusiasm for Roctavian, the SVB team said.

Before the FDA decision, the European Commission had approved Roctavian in August last year. In the EU, BioMarin is working to launch the drug first in Germany. A separate SVB survey suggested Roctavian may have big potential in Europe.

Editor's Note: The story has been updated with additional information shared during an investor call Thursday.