The Food and Drug Administration on Tuesday approved the first gene therapy for a type of hemophilia, giving people with the inherited disorder a treatment option that could potentially keep their bleeding in check for years while also allowing them to skip the infusions that have been the standard of care.
The therapy, called Hemgenix and developed by the Dutch biotechnology company UniQure, is for the less common “B” form of hemophilia, which is estimated to represent about 15% of all patients with the disease.
“Gene therapy for hemophilia has been on the horizon for more than two decades,” said Peter Marks, head of the FDA’s Center for Biologics Evaluation and Research, in a Tuesday statement. “Today’s approval provides a new treatment option for patients with hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”
Australian drugmaker CSL, which licensed Hemgenix from UniQure and will market the drug, set the treatment’s list price at $3.5 million, making it the most expensive medicine in the U.S. on a single-use basis.
In a statement, the company said it is confident that the price “will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of hemophilia B.”
The Institute for Clinical and Economic Review, an influential nonprofit that assesses drug costs, previously estimated Hemgenix could be cost effective at a price of $2.9 million. The group cited the therapy’s benefit in clinical testing, as well as the high cost of current treatment.
Hemophilia B is caused by missing or low levels of a critically important protein called Factor IX that the body needs to effectively clot blood. Depending on the amount of Factor IX present, people with the condition experience spontaneous or excessive bleeding that can cause serious health complications.
To prevent this, treatments consisting of replacement Factor IX are taken routinely — a regimen that many patients consider burdensome to daily living. (While women can have hemophilia B, most individuals who experience symptoms are men.)
“Anecdotally, what we hear from the gentlemen who have gone through this treatment is they’re really enjoying not having to think about their hemophilia anymore,” said Steven Pipe, a professor of pediatrics and pathology at the University of Medicine who led the main trial testing Hemgenix. “You’re not doing infusions anymore. You’re not scheduling your life around your prophylactic therapy.”
In that study Pipe helped run, 54 adult men with severe or moderately severe hemophilia B were given Hemgenix and tracked for changes in their Factor IX levels, as well as bleeding rates and use of standard replacement therapies.
After 18 months, treatment raised Factor IX levels to amounts that were, on average, typically considered equivalent to “mild” hemophilia. The annualized bleeding rate was sharply reduced and participants were largely able to stop taking replacement Factor IX.
Meant to be a one-time treatment, Hemgenix is designed to replace the gene that encodes for Factor IX and is defective in people with hemophilia B. A specially engineered virus, known as AAV5, is used to shuttle a functioning version of the gene into the liver, where it’s taken up by cells and spurs production of Factor IX.
Its development has been years in the making. Hemophilia was one of the first diseases identified as a good candidate for gene therapy. A landmark 2014 study of a treatment similar to Hemgenix showed the potential for long-term bleeding control.
UniQure, which was originally known as Amsterdam Molecular Therapeutics, extended that research, first developing and testing a prototype gene therapy using the AAV5 virus. It then tweaked that version further to make what’s now approved as Hemgenix. (In testing, Hemgenix was known as AMT-061, or etranacogene dezaparvovec.)
In 2020, UniQure sold rights to Hemgenix to CSL for $450 million upfront, with additional payments promised depending on the achievement of regulatory and commercial milestones.
Development was stalled, however, by a case of liver cancer in one study participant, which prompted the FDA to temporarily suspend testing. UniQure later determined the cancer was unrelated to treatment, but the delays pushed back when it and CSL applied for regulatory approval.
Michigan’s Pipe noted that many people with hemophilia have hepatitis C or other liver problems that raise their risk of cancer. He pointed to the longer follow-up for participants in the 2014 study and the earlier work UniQure did with Hemgenix’s predecessor as further evidence of the low cancer risk.
“We still need to do epidemiological follow-up on a global scale for patients who undergo gene therapy to make sure that we don't see some accumulating safety signal in malignancy or any other adverse event risk,” he said.
CSL said it plans to make Hemgenix available immediately. The therapy is also under review in Europe. There, European regulators have approved a gene therapy from BioMarin Pharmaceutical for the more common hemophilia A.
The FDA is set to make a decision on BioMarin’s treatment, called Roctavian, next year. The agency originally planned to consult an advisory committee, but on Wednesday the company disclosed the FDA is no longer planning to do so.
Editor’s note: This story has been updated with additional detail throughout and to reflect BioMarin’s announcement on Wednesday.