New Gene Therapy Could Face Uphill Battle
- Potential FDA approval of BioMarin’s gene therapy for hemophilia would be major win, but uptake could be slow
Gene therapies are having a good run, though hurdles remain.
In recent weeks, the U.S. Food and Drug Administration has approved two new therapies, one for a genetic skin disorder developed by Krystal Biotech and another for a crippling muscle condition made by Sarepta Therapeutics. By Friday, another treatment could get the green light.
If the much-delayed FDA approval for BioMarin Pharmaceutical’s gene therapy Roctavian for hemophilia A is granted, it would mark an impressive streak for an industry that is still in its infancy and has faced numerous struggles, from safety concerns to manufacturing hurdles. It would also be a relief for BioMarin and its investors, who have waited nearly three years since the FDA rejected the drug in August 2020, citing the need for longer-term data.
But an FDA nod, which analysts see as likely, doesn’t mean it will be smooth sailing for the therapy.
The big issue for BioMarin is that, unlike certain rare genetic diseases where patients have limited options, hemophilia patients—who suffer from a rare blood disorder that stops blood from clotting properly—do have available treatments. Options include Factor VIII replacement therapies, which replace patients’ missing clotting factors with clotting factor concentrates, and Roche Holding’s Hemlibra, a blockbuster antibody that analysts expect will generate nearly $5 billion in sales this year. The factor replacement therapies must be given intravenously several times a week, a major inconvenience, while Hemlibra can be administered monthly, which is still not ideal. A one-time therapy that can deliver a copy of the gene that is faulty in people with hemophilia offers a major advance for patients.
One challenge, however, is that clinical trial data shows the treatment’s effects tend to wane over time, so the therapy doesn’t seem to represent a long-term cure. When the treatment wears off, patients would essentially have to go back to the therapies they were on. And, because the viral makeup of the therapy essentially primes the immune system to attack it next time it sees the same therapy, patients often can receive a treatment only once, raising the stakes of a decision.
Most patients will likely opt to wait, given there are other gene therapies currently being developed that could potentially offer a better risk-benefit profile one day, said Kostas Biliouris, an analyst at BMO Capital Markets. “Hemophilia A isn’t a deadly disease and patients have a great drug available to them, Hemlibra," he said.
Jared Holz, a healthcare equity strategist at Mizuho, said there is some investor concern that doctors will be reluctant. “You’re transitioning patients from an existing therapy to gene therapy that may not work past five years," he said. “Is that compelling enough for doctors to make the switch?"
Still, approval of Roctavian would be a major win for some patients, particularly those with the most severe form of the disease, who are at risk of life-threatening bleeding. Though it may initially cost over $2 million per treatment, it could actually save the healthcare system money over time because Hemlibra’s net price can exceed $600,000 annually.
And to make it work financially, the company doesn’t need to treat that many patients. Just 100 patients a year at such nose-bleeding prices would turn this into a relatively large business. BioMarin estimates that worldwide there are more than 20,000 adults affected by severe hemophilia A. In its latest earnings call, management said the company has engaged with around 300 U.S. patients who want to learn more about the therapy. Analysts polled by FactSet see the therapy reaching more than $1 billion in sales by 2028.
But the company’s experience in Europe doesn’t augur particularly well for getting to that billion-dollar range anytime soon. While Roctavian was granted conditional approval in Europe last August, it had yet to dose a single patient as of the first quarter. During its first-quarter earnings call in April, the company said it was still finalizing agreements with payers in Europe and lowered its Roctavian sales guidance for 2023 to between $50 million and $150 million.
Ups and downs are to be expected in what is essentially a medical revolution. For BioMarin, finally securing an FDA approval after years of delays will be a major victory and it should provide an initial bump to a stock that has traded essentially flat for years. But for long-term investors, strong patient uptake, rather than an FDA approval, could be a better signal for an entry.
Write to David Wainer at david.wainer@wsj.com
