Hemophilia B: Post-Beqvez, What's Next for Gene Therapy?

Medscape

12-05-2025

In the spring of 2024, the US Food and Drug Administration (FDA) approved fidanacogene elaparvovec (Beqvez), only the second gene therapy product for hemophilia B. Just a few months later, the Pfizer treatment — expected to cost $3.5 million for a one-time dose — got a boost from a phase 3 study published in The New England Journal of Medicine that found annualized bleeding rates fell by 71% in 45 treated men, although 21% resumed prophylaxis.
Then, in April 2025, a follow-up analysis of patients from a phase 1-2a study appeared in NEJM . It tracked 14 patients for at least 3 years and reported none had serious treatment-related adverse events after year 1.
The newer findings were good news, but they came too late to matter. Pfizer had killed off Beqvez 2 months earlier.
'The company said the discontinuation was due to several reasons,' Reuters news service reported, 'including limited interest in gene therapies for the bleeding disorder.' (Pfizer had earlier dumped a gene therapy for hemophilia A, also blaming a lack of interest.)
In fact, it appears that Beqvez was never administered outside clinical research.
What does the loss of this treatment mean for the estimated 7250 patients with hemophilia B in the United States and the hematologists who treat them? Here are some questions and answers about the state of gene therapy in hemophilia B.
How Does Gene Therapy for Hemophilia Work?
Gene therapy, which is now FDA-approved for hemophilia A and hemophilia B, deliver genes for factor VIII or IX via adeno-associated viruses. The liver then begins producing factor, potentially allowing patients to stop or reduce their use of prophylactic therapy.
'In the best-case scenario, [gene therapy] will provide factor levels in the normal range and essentially normal hemostasis without having to give yourself medication for many years,' explained pediatric hematologist Benjamin Jacob Samelson-Jones, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia, both in Philadelphia, in an interview for a January 2025 Medscape Medical News article.
What Made Beqvez Unique?
Not a lot compared with its sole competitor. The FDA approved etranacogene dezaparvovec (Hemgenix), the first gene therapy for hemophilia B, in November 2022. It remains available.
Beqvez required a smaller dose, and this was thought to be a potential benefit, said hemophilia specialist Steven Pipe, MD, professor of pediatrics and pathology at the University of Michigan, Ann Arbor, Michigan, in an interview.
'There was a hypothesis that lower dosing could provide a theoretical safety advantage — less vector-related toxicity that may manifest with liver toxicity or the overall number of DNA integration events.' (In gene therapy, 'potential integration of therapeutic transgene into host cell genomes is a serious risk' that can lead to mutations and the creation of tumors, according to a 2023 report.)
Safety data have not shown a 'clear signal' of a difference in liver toxicity between the therapies, Pipe said. 'Still, we had hoped that clinicians could have a choice to put before patients.'
Were There Other Differences Between Beqvez and Hemgenix?
According to Pipe, 'the patient eligibility is reduced compared to Hemgenix since it requires patients to have neutralizing antibody (Nab) titers < 1:5 against the SPK100 vector. Best estimates are that 60% of those screened would be eligible. Nab positivity was not an exclusion for Hemgenix.'
The costs for the treatments were both around $3.5 million.
Why Didn't Beqvez Catch On?
'There are probably multiple reasons for this, including high cost, logistical challenges for centers wanting to offer gene therapy, caution on the part of patients about long-term safety, and the availability of other good treatment options,' said Adam Cuker, MD, professor of medicine in the Department of Pathology and Laboratory Medicine and chief of the Section of Hematology at the University of Pennsylvania, in an interview. He led the 2024 NEJM phase 3 study of Beqvez.
In an interview, Samelson-Jones said it's a shame that Beqvez left the market. 'Worldwide, having two safe and very effective gene therapies for hemophilia B would have decreased costs and increased patient access in the long run. To me, this is why this is a loss to the community.'
How Do Competing, Non-Gene Therapy Treatments Fit Into the Picture?
The FDA recently approved several new subcutaneous treatments as therapies for both hemophilia A and hemophilia B: Marstacimab (Hympavzi), fitusiran (Qfitlia), and concizumab (Alhemo). 'These drugs add to the growing list of treatment options for patients with hemophilia B,' Cuker said. 'It would not be surprising if some patients who otherwise would have been interested in gene therapy choose one of these subcutaneous treatments instead.'
Subcutaneous therapy 'may decrease treatment burden enough that a one-and-done treatment like gene therapy is less attractive,' Samelson-Jones said. 'Hympavzi and other new nonfactor therapies may be a bridge that patients want to try before committing to gene therapy. However, nothing prevents bleeding like factor IX, which is what gene therapy provides.'
What Should Hematologists Know About Gene Therapy in Hemophilia B?
'The data for gene therapy in hemophilia B are robust,' Cuker said. 'They show impressive efficacy with a durable response in most patients and a favorable safety profile. For my patients who have received gene therapy, the results have been nothing short of life-changing.'
He added: 'Patients with hemophilia B deserve to hear about gene therapy as a treatment option from their hemophilia provider. If a patient is potentially eligible for and interested in gene therapy and it is not offered at their home institution, they should be referred to a center with expertise and experience in gene therapy.'
What's Next for Gene Therapy in Hemophilia B?
Regeneron is exploring second-generation factor IX gene therapy that relies on gene editing, Pipe said. 'This protocol is looking to establish durable, stable expression. If safe and effective, it has the potential to treat pediatric patients.'
An ongoing trial seeks to enroll 120 patients and to conclude by April 2026.
Meanwhile, another therapy under investigation 'harvests the patient's own B cells by apheresis,' Pipe said. 'The cells are gene edited at a manufacturing facility so that they express factor IX, then the cells are differentiated to long-lasting plasma cells and given back to the same patient. No immunosuppression required since this is autologous cellular therapy.'
This therapy 'as the potential for repeat treatment if expression declines over years and can also be dose-titrated to desired expression level,' Pipe said.
Be Biopharma has begun a trial of this therapy.