BioMarin's hemophilia gene therapy Roctavian wins conditional EU backing amid FDA delay

The future of BioMarin’s first-of-its-kind hemophilia gene therapy remains uncertain at the FDA, but its regulatory path in Europe now looks clearer.

The European Medicines Agency has recommended granting a conditional approval to BioMarin’s Roctavian, also known as valoctocogene roxaparvovec, to treat patients with severe hemophilia A who do not have factor VIII inhibitors, the European regulator said Friday. Patients should also test negative for antibodies to the adeno-associated virus serotype 5, which serves as the vector for the gene therapy.

The positive opinion sets Roctavian up for an official European Commission approval in the third quarter, BioMarin said. As the California biotech noted, Roctavian is on track to be the first gene therapy available in Europe for hemophilia A.

The company expects its first rollout in Germany with a reimbursment agreement in place right after a potential approval, BioMarin Chief Commerical Officer Jeff Ajer told investors during a conference call Friday.

The EMA green light comes as BioMarin has yet to refile Roctavian with the FDA. Less than a month ago, the company postponed plans to resubmit an FDA application to September, saying the U.S. agency has requested additional information.

Back in 2020, the FDA surprisingly turned down Roctavian, demanding longer, two-year annualized bleeding rate data from a phase 3 clinical trial. BioMarin shared those data in January and at that time laid out a plan to knock on the FDA’s doors again in the second quarter.

Now the positive EMA opinion bodes well for Roctavian in the U.S., SVB Securities analyst said in a Friday note.

As the EMA noted, currently available hemophilia A treatments require lifelong repeated injections. Roche’s Hemlibra, a leading antibody drug, can be taken up to once every four weeks.

“Therefore, there is an unmet medical need for new therapeutic approaches that might free patients from frequent injections,” the EMA said in a statement.

Enter Roctavian. It uses AAV5 to carry functional factor VIII genes into the liver cells to replenish the missing blood-clotting protein. BioMarin is proposing Roctavian as a one-time therapy, but questions remain about the drug’s long-term efficacy.

In Roctavian’s phase 3 trial in 134 patients, the average annualized bleeding rate fell 85% from its baseline to less than one episode in the second year after treatment. BioMarin also submitted five-year data from a small early-phase trial, which the EMA said supported its treatment effect.

Nevertheless, the EMA said it’s unknown how long the effect from a single infusion will last in a patient. “Longer-term follow-up tests may be required to verify a continued safe and effective response to the medicine,” the EMA said of Roctavian.

Once Roctavian is officially approved, patients will be monitored for 15 years to ensure the long-term efficacy and safety of this gene therapy, the agency added.

BioMarin has already started reimbursement talks with each country, Ajer said. The company is eying outcome-based payment deals, which could entail returning the full cost if a patient doesn’t respond to treatment, or some of the cost if a patient stops benefiting over time.

Industry watchers have already picked up on a signal of waning efficacy from the endogenous factor VIII activity level, which dropped in Roctavian’s clinical trials as time went by.

Getting across the regulatory finish line is important, the SVB team said, but “it is just as important for BioMarin to fortify its relationships with hemophilia treatment centers given that the adoption of Roctavian requires physicians' willingness to help since it requires close patient monitoring and is a procedure to administer Roctavian.”

Recent market research showed that healthcare professionals in EU estimated Roctavian could capture 35% of eligible patients, in line with BioMarin’s own projection, Ajer said. Plus, about 80% of surveyed doctors in both EU and the U.S. expect to treat at least one patient with Roctavian within 12 months of an approval, he added.

Editor's Note: This story has been updated with additional information from a BioMarin investor call.