BioMarin, a California-based biotechnology company, said Wednesday that its gene therapy for hemophilia has been cleared for market by European regulators, marking a first-of-its-kind approval.
The therapy, known as Roctavian, was given conditional marketing authorization as a treatment for certain patients with hemophilia A, the more common version of the rare bleeding disorder. Specifically, Roctavian is to be used in adults with “severe” disease — hallmarked by exceedingly low levels of a blood-clotting protein called Factor VIII — who don’t have a history of developing antibodies that attack this protein.
Roctavian delivers a functional copy of the Factor VIII-producing gene into cells via a modified virus, so, to be eligible for treatment, patients must also test negative for antibodies that would defend against that virus.
With approval in hand, BioMarin is now working to secure reimbursement across the European Commission’s various member states. Jeff Ajer, the company’s chief commercial officer, said on a conference call Thursday that the plan is to immediately launch Roctavian in Germany, followed by France. The company expects Roctavian’s list price in Europe to be “around” 1.5 million euros, or roughly $1.5 million, net of all discounts, he said.
Ajer added that BioMarin expects to disclose the specific European list price in October, a number that will be in-line but lower than the comparable net price in the U.S.
"This approval in the EU represents a medical breakthrough in the treatment of patients with severe hemophilia A that expands the conversation between a patient and physician,” said Johannes Oldenburg, director of the Hemophilia Centre at the University Clinic in Bonn, Germany, in a statement from BioMarin. "It is exciting to imagine the possibilities of this approved gene therapy, which has demonstrated a substantial and sustained reduction in bleeding for patients, who potentially could be freed from the burden of regular infusions.”
Hemophilia patients, especially those with severe disease, undergo regular infusions of engineered Factor VIII to prevent or treat episodes of uncontrolled bleeding. These treatments can be expensive and, to some, burdensome. They also aren’t foolproof, as patients can still have bleeds.
Gene therapy has emerged as a potential solution to these problems. Framed as a one-time treatment, proponents argue that gene therapy, if proven safe and effective, could improve the livelihoods of hemophilia patients while saving the healthcare system considerable costs — even when priced at a relatively large amount.
According to BioMarin, the European Commission made its decision based on data the company collected over the better part of the last decade. BioMarin’s application included results from an early-stage study that, after four to five years of follow-up, showed treatment with Roctavian reduced average annual bleeding rates by more than 90% and average yearly use of Factor VIII replacement therapy by at least 95%.
Two-year data from a larger, late-stage study found a similar benefit, though the levels of clotting protein in these participants also appeared to wane over time.
The durability of Roctavian and other hemophilia gene therapies in development has been a focal point for regulators, including the Food and Drug Administration, which, in August 2020, turned down an approval request from BioMarin. In announcing the rejection, the company said the agency wanted at least two years of follow-up data on each patient in that larger study before approval could be considered.
Following another unexpected delay, BioMarin has said it plans to refile an application with the FDA in September.
Though BioMarin has accomplished a rare feat in biotech, ushering seven products to market, it hasn’t been profitable during the vast majority of its 25-year history. Roctavian, though, may provide a substantial lift to the company’s bottom line. For example, in a note to clients Thursday, SVB Securities analyst Joseph Schwartz wrote that his team forecasts $2.2 billion in peak yearly sales of the gene therapy.
On Thursday’s conference call, Ajer said recent market research suggests that approximately 35% of eligible patients in Europe would receive Roctavian. The company estimates there are 8,000 adults with severe hemophilia A across the 24 European countries affected by Wednesday’s approval, 3,200 of whom would be eligible for Roctavian treatment.
“We do anticipate some pent-up demand will drive initial sales in the fourth quarter of this year, and expect an increasing uptake of volume beginning in the first quarter of next year,” Ajer said.
After Germany and France, BioMarin intends to roll out Roctavian in Italy, Spain, and then other countries. Ajer said outcomes-based agreements with payers — in which the price is tied to the drug’s performance — will be negotiated on a market by market basis, though the goal of each will be to guard against the risk of a “non-response” to treatment for at least five to eight years.
As part of the conditional authorization, BioMarin must submit additional results from ongoing studies of Roctavian. That includes five years of data from the larger, late-stage study, as well as two-year results from a newer trial evaluating the safety and effectiveness of Roctavian with prophylactic steroid use. The latter trial has completed enrollment, BioMarin said.