In 2022, when the first gene therapy for hemophilia received approval from the Food and Drug Administration (FDA), many in the bleeding disorders community hailed it as a transformative breakthrough — a potential “one-and-done” treatment that might eliminate the need for regular prophylactic clotting factor infusions.
Four years later, adoption of this revolutionary therapy has been much slower and more cautious than people had hoped. In fact, due to low demand and other issues, the manufacturers of two of the FDA-approved gene therapies for hemophilia — Beqvez for hemophilia B and Roctavian for hemophilia A — have withdrawn those products from the market.
Only Hemgenix for hemophilia B remains (although the manufacturer announced in March 2026 that it would be temporarily unavailable due to a supply issue related to the complexity of manufacturing gene therapy).
Why hasn’t gene therapy taken off the way it was expected to? Experts say there are several reasons for the slow uptake:
- Concerns about waning efficacy with gene therapy for hemophilia A
- High upfront costs (upward of $3.5 million per dose) as well as insurance denials and red tape
- Increased competition from newer factor and nonfactor treatments
These reasons are prompting many people with hemophilia A (which is three to four times more common than hemophilia B) to take a wait-and-see approach. They’re wary of trading a known routine that’s working well for an expensive one with unknown long-term durability.
Experts say that reluctance is not unique to gene therapy. “I think our community is a little hesitant to embrace any type of new therapy without a lot of research and passage of time,” says Brendan Hayes, senior director of education and innovative therapies at the National Bleeding Disorders Foundation (NBDF).
Hematologist Mark Reding, M.D., director of the M Health Fairview Center for Bleeding and Clotting Disorders at the University of Minnesota in Minneapolis, agrees. “No new therapy in hemophilia has ever taken off like gangbusters,” he says. “It’s been a slow uptick for all of them, and I think it’ll continue to be that way.”
How Gene Therapy for Hemophilia Works: The Promise vs. The Reality
Gene therapy for hemophilia works by giving the body a functioning copy of the missing or faulty gene — factor VIII for hemophilia A or factor IX for hemophilia B — so the liver can start making more of that clotting factor on its own.
The healthy gene is packaged inside a vector, which you can think of as a tiny delivery vehicle. Current treatments use an AAV (adeno-associated virus) vector: a harmless virus that has been modified to carry the gene into liver cells and is given by IV infusion. The goal is to deliver enough working copies of the gene to the liver that people can greatly reduce — and possibly even stop — regular preventive treatments.
While the results for gene therapy for hemophilia B have been encouraging, the story for hemophilia A has been more complicated. In an April 2026 NBDF webinar, Benjamin J. Samelson-Jones, M.D., Ph.D., associate director of Clinical In Vivo Gene Therapy at Children’s Hospital of Philadelphia, explained the difference in outcomes for gene therapy for hemophilia A versus hemophilia B.
With hemophilia B, factor IX levels after gene therapy tend to stay steady for many years. With hemophilia A, factor VIII levels “are tied up in a Gordian knot — either you have high but declining levels or low but stable levels,” Samelson-Jones said in the webinar. Either way, it’s not the long-term, steady protection that everyone hoped for.
In an interview, Samelson-Jones explained a key difference between the two gene therapies: “The products we have now for hemophilia B are probably second or third-generation,” he says. “What we have for hemophilia A is really the first generation, so it’s not surprising that the overall outcomes of a first-generation product don’t quite stack up.”
The Economics of Gene Therapy
The extremely high cost of gene therapy adds another layer of friction, experts say.
As Nathan Schaefer, NBDF’s senior vice president of public policy and access, points out, the real burden falls less on patients than on the insurance system that decides who can access gene therapy. “The price is significant, but it’s not like a patient has to dole out millions of dollars,” he says.
Instead, the pressure lands on insurance companies who must justify covering such an expensive, one-time treatment for people who may not keep their policy very long. “There are data that show very clearly that gene therapy for hemophilia B is cost-effective after a few years,” Schaefer says. “The challenge from a payer perspective is whether that patient is going to remain on that payer’s plan for the duration of the effectiveness of the treatment.”
According to Schaefer, NBDF has seen insurance companies imposing inconsistent and sometimes dangerous coverage parameters. “There are significant concerns when it comes to the criteria that payers are requiring for people to become eligible for gene therapy, some of which would literally put patients’ lives at risk,” he says. “We’ve seen some plans say you have to demonstrate 12 bleeding episodes in one year. No hematologist would ever consent to letting their patient bleed that much so that they then qualify for gene therapy.”
NBDF has also heard of inconsistent approval criteria based on the state someone lives in or on their age, Schaefer says. “An insurer is possibly more likely to approve gene therapy for somebody who’s 20 years old versus somebody who’s 63 years old because they're going to get more bang for their buck,” he says.
To encourage health insurers to become more comfortable with paying for costly gene therapies, Hayes says NBDF and other policy groups are exploring models that link payments with real-world results. “We’re looking at things like warranties — where reimbursement is based on how the therapy is actually performing,” she says. Another strategy that payers may use is reinsurance, in which they transfer a portion of their financial risk to a secondary insurer to limit their overall liability.
A Crowded Hemophilia Treatment Market
The current expanded hemophilia treatment landscape is another reason interest in gene therapy is not as robust as expected, Reding says.
“When gene therapy started out, the comparator was standard half-life factor, so the bar was not that high,” Reding says. “Today, gene therapy is competing with many other treatments.”
For example, there are now extended half-life factor products, which enable higher levels of factor to stay in the body for longer, resulting in the need for less-frequent infusions. There are also rebalancing agents, which are administered with subcutaneous injections rather than intravenous infusions.
“The target keeps moving,” Reding says, making it harder for both clinicians and patients to decide whether gene therapy is worth trying.
Samelson-Jones predicts that, at least for patients with hemophilia B, there will be a “slow tidal wave” as more people who have received gene therapy share their experiences with others.
“More than 90% of people are successful and don’t need anything else,” he says, “so I think that will prompt more people who were initially hesitant to decide that they’re ready to move forward.”
What’s Coming Next for Hemophilia A Gene Therapy
In the NBDF webinar, Samelson-Jones called 2026 “the end of the beginning of gene therapy for hemophilia,” with he and others in the field now focused on fixing some of the shortcomings of the first-generation hemophilia A gene therapy.
The big goal, he explained, is to make gene therapy for hemophilia A work more like it does for hemophilia B. To get there, his team is taking what he calls a “Robin Hood” approach to gene therapy — borrowing from people whose bodies naturally make too much clotting factor and using those genetic clues to help people who don’t make enough.
One key strategy is to redesign factor VIII so that it works harder without needing to make as much of it. Samelson-Jones says these “gain-of-function” factor VIII variants are “bioengineered to improve the potency of gene therapy for hemophilia A.”
The hope, he says, is that this Robin Hood strategy can “cut this Gordian knot” of either high-but-falling or low-but-stable factor VIII levels and move hemophilia A gene therapy closer to the goal of providing “safe, durable factor expression at a level sufficient to prevent bleeding in all recipients of the gene therapy.”
While Samelson-Jones’ research is still in its early stages, for many in the bleeding disorders community, it’s a concrete reason to believe that a safer, longer-lasting gene therapy for hemophilia A is on the horizon.
“There have been complications and complexities,” Schaefer says, “but we want people in our community to know that there is more hope for gene therapy in the future.”