After prior rejection, BioMarin tries again with hemophilia gene therapy in the US

With a recent European nod and multiple years of durability data in the books, BioMarin Pharmaceutical is finally getting a second shot at approval for its gene therapy valoctocogene roxaparvovec in the U.S.

Late this week, the company said it had resubmitted its FDA application for the drug, also known as Valrox, to treat adults with severe hemophilia A. The FDA is expected to accept or reject BioMarin’s resubmission by the “end of October,” the company added.

The drug, which snared a hemophilia green light as Roctavian in Europe this past August, is in the running to become the first gene therapy approved for the bleeding disorder in the U.S.

But ValRox certainly hasn’t had an easy path to regulators’ desks.

BioMarin’s resubmission comes in the wake of an August 2020 rejection, when the FDA handed down a complete response letter amid concerns about the longevity of Valrox’s effect.

The agency asked BioMarin to finish off its phase 3 study and tender an additional two years of follow-up safety and efficacy data on all participants.

In its resubmission announcement, BioMarin pointed out that the revised Valrox application includes the company’s response to the CRL plus “two-year outcomes from the global GENEr8-1 Phase 3 study and supportive data from five years of follow-up from the ongoing Phase 1/2 dose escalation study.”

As for when ValRox’s green light could come stateside, BioMarin explained that biologics license application submissions are typically followed by a six-month review period. With that in mind, the company thinks the FDA may need another three months on top of that “based on the number of data read-outs that will emerge during the procedure.”

That proposed timeline pushes a potential approval out to around 2023’s second quarter.

BioMarin had originally planned to resubmit Valrox to U.S. regulators in June, but its plans were further delayed this summer when the company reported it had received additional questions from the FDA. BioMarin was vague on what the FDA asked for, stating the agency had requested additional details and analyses rather than more studies.

Still, Valrox has fared better across the pond, where the EU bestowed conditional marketing authorization upon the drug late last month.

Even with that win, BioMarin will have its work cut out convincing overseas payers of Roctavian’s hefty price tag, which Evercore ISI analysts previously reported to be in the vicinity of 1.5 million euros.

To start, BioMarin will launch in Germany, where the company expects to begin commercial dosing in the fourth quarter. The company could be looking at about 600 to 700 eligible patients early on, the Evercore team wrote to clients at the time of approval.

Valrox is one of two “transformational” launches for BioMarin, CEO Jean-Jacques Bienaimé said last summer. The other arrow in the company’s quiver is its achondroplasia treatment Voxzogo, which launched in the U.S. following an approval in November 2021.