Experts Debate Scope of Access to Gene Therapy for Patients With Hemophilia

At a friendly debate held at the European Hematology Association 2024 Congress, hemophilia experts argued for and against wider access to gene therapy for patients living with the condition.

Gene therapy represents a game-changing innovation that can effectively treat hemophilia in one dose by replacing a faulty gene with a functional one, but disagreement exists over whether it should be offered to all patients, as evidenced by a debate session taking place at the European Hematology Association 2024 Congress.

The stage at the EHA2024 Congress where the debate took place | Image Credit: © Christina Mattina

The stage at the EHA2024 Congress where the debate took place | Image Credit: © Christina Mattina

Chairing the session were Riitta Lassila, MD, PhD, professor at University of Helsinki, and Brian O’Mahony, chief executive of the Irish Hemophilia Society. They kicked off the debate by polling the audience on their likelihood of recommending gene therapy to their patients: for hemophilia A, the responses were 0% very likely, 71% likely, 14% unlikely, and 14% very unlikely, whereas for hemophilia B they were 0%, 62%, 23%, and 15%, respectively.

Taking the stage in hopes of shifting the audience more toward that likelihood, Ana Boban, MD, professor at University Hospital Centre Zagreb in Croatia, first explained that hemophilia is highly suitable for gene therapy, as a monogenic disease with a clear target, in which bleeding phenotypes are responsive to factor levels and efficacy can be assessed by quantifiable end points. A single intravenous administration of gene therapy can result in sustained and durable expression of factors XIII or IX, which can lead to better control of bleeding, the ability to discontinue prophylaxis, and improvement in quality of life (QOL).

Recent findings have supported this potential, with Madan et al observing that 87% of patients with hemophilia A did not require prophylaxis 3 years after valoctocogene roxaparvovec receipt1 and von Drygalski et al finding stable and durable factor IX levels over 4 years after etranacogene dezaparvovec administration in patients with hemophilia B.2 Other data have shown encouraging outcomes for gene therapy in terms of a very low annualized bleeding rate, high percentages of patients experiencing no bleeds requiring treatment or no bleeds at all, and very low factor IX consumption among those with hemophilia B.3

The QOL gains that this one-time therapy can provoke are equally exciting, as instead of experiencing high treatment burden with frequent factor replacement, doctor’s visits, and filling prescriptions, patients can instead get closer to achieving the “hemophilia-free mind,” where they no longer need to plan their life around their disease, Boban said.

She wrapped up her pitch by showing a photo of the Erasmus Bridge in the Netherlands, the home base of the next speaker. The bridge connects the older part of Rotterdam with the more exciting part of the city with museums and nightlife. Similarly, she said, we shouldn’t stop patients from crossing that bridge into a hemophilia-free mind with the help of gene therapy. “Who wants to cross? I think everybody: patients with hemophilia A, patients with hemophilia B, young patients, old patients, even women with hemophilia. All patients with hemophilia should have access to gene therapy.”

“If you want to cross the bridge you have to be well informed, because sometimes the bridge is open and the water is very cold,” countered Frank Leebeek, MD, PhD, chair of the Department of Hematology at Erasmus Medical Center, to explain his hesitation around offering gene therapy to all patients with hemophilia. Some specific reasons for this caution included the following:

  • Longer-term data are not yet available, particularly on any association between gene therapy and malignancy.
  • Gene therapy carries a risk of liver abnormalities, which require a long course of steroids.
  • Not all patients achieve a response after gene therapy, and redosing is not possible for these patients. The same recent data cited by Boban indicate that 13% of participants had to resume prophylaxis for their hemophilia A after valoctocogene roxaparvovec gene therapy—a nontrivial proportion.1
  • There are limited data on patients who have been excluded from clinical trials, such as children, women, and those with liver disease.
  • Patient adherence can be an issue, as they must abstain from alcohol and complete an intensive monitoring regimen.
  • Finally, a significant barrier to expanding access is the bill for gene therapy, with the cost reaching €2.8 million for one 30-minute infusion.

Considering that exorbitant cost, that there are other treatment options available, and that he cannot make guarantees to his patients regarding factor levels, durability of response, and long-term effects, “I think it should only be for a few and I don’t know if they’re the happy few,” Leebeek said.

In response to a question from the audience about which patients constitute these lucky few, Leebeek explained that adult male patients with hemophilia B who have a high current burden of treatment are likely most suitable for gene therapy. Boban agreed but added that even patients with hemophilia A may find it worthwhile to take the one-shot treatment if they have difficult venous access and want to take the chance on achieving the hemophilia-free mind.

When the audience was polled again on their likelihood of recommending gene therapy to patients, the answers had shifted toward more enthusiasm, with 18% and 36% saying they would be very likely or likely to recommend it for hemophilia A and 33% and 26%, respectively, endorsing it for hemophilia B. On viewing these results, Leebeek conceded to Boban with a congratulatory handshake.

He acknowledged that he has treated 5 of his own patients with gene therapy and heard glowing responses, with one saying to him, “‘Frank, if I ever need prophylaxis again, then at least I had 5 years without hemophilia.’ And he’s still very thankful for that.”


1. Madan B, Ozelo MC, Raheja P, et al. Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A. J Thromb Haemost. Published online April 12, 2024. doi:10.1016/j.jtha.2024.04.001

2. von Drygalski A, Pipe SW, Giermasz A, Gomez E, Monahan PE, Le Quellec S. Stable and durable factor IX levels over 4 years after etranacogene dezaparvovec gene therapy administration in a Phase 2b trial in patients with haemophilia B. Haemophilia. 2024;30(S1):PO038. doi:10.1111/hae.14919

3. Klamroth R, Bonner A, Gomez K, et al. Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B. Haemophilia. 2024;30(1):75-86. doi:10.1111/hae.14882

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