Single-dose gene therapy is potentially life-changing for adults with hemophilia B

Hemophilia is a genetic disorder that limits the blood's ability to clot and affects around 30,000 people in the United States, mostly males. Left untreated, it can cause spontaneous bleeding, particularly internal bleeding into the joints, which, over time, can cause painful joint damage and mobility issues. Hemophilia B is caused by a lack of clotting factor IX. The gene therapy enables the liver to create factor IX, which allows the blood to clot and protects patients from frequent bleeds.

"What we saw from patients in this study was that within a few days of receiving the gene therapy infusion, it took root, and their bodies started making factor IX for the first time in their lives," said study investigator and lead author Adam Cuker, MD, MS, section chief for Hematology, and clinical director of the Penn Blood Disorders Center and the Penn Comprehensive Hemophilia Program. "We always want to be careful about using the word 'cure' especially until we have longer follow-up data, but for many of these patients, it's been life changing."

After at least one year of follow-up, participants in the study had an average 71 percent reduction in bleed rate after receiving the gene therapy, compared to the year prior, when they were treated with prophylactic infusions of factor IX, the standard treatment for the disease. More than half of the 45 patients in the study did not have any bleeds after receiving gene therapy.

FDA-approved gene therapies available at Penn Medicine

Based on the results of this study, the FDA approved the gene therapy (fidanacogene elaparvovec) in April 2024. Cuker was the site lead for the clinical trial at Penn Medicine, which was one of the top-enrolling sites for the study. It represents the second form of gene therapy approved to treat hemophilia B. The first such therapy (etranacogene dezaparvovec-drlb) was approved in November 2022, and Penn Medicine is one of several medical centers in the United States where this treatment is available to patients.

Gene therapies have very specific guidelines that determine eligibility and require specialized knowledge to carry out patient screening and selection, education about treatment risks and benefits, and post-therapy monitoring. Penn Medicine offers access to numerous clinical trials for gene therapy and expertise in administering FDA-approved gene therapies.

In the current study, the most common adverse effect was related to an immune system attack on liver cells that were targeted by the gene therapy, which can render the gene therapy ineffective, if not quickly treated. In the study, affected patients were treated with steroids to limit this immune reaction. Patients in the study will continue to be followed for at least five years to monitor potential long-term side effects.

Life-changing impact

For patients with hemophilia B, the current standard of care of ongoing prophylactic infusions of factor IX is generally effective, but burdensome. Depending on the specific product, a patient may require regular infusions anywhere from once every two weeks up to several times a week. Most patients learn how to put their own IV in to be able to complete their infusions at home. The goal of this prophylactic treatment is to regularly give the body enough factor IX to prevent bleeds, though they still occur. By contrast, the new gene therapy only requires a single dose, and most patients in the study did not need to resume prophylactic factor IX treatments.

"We hear from people born with hemophilia that -- even if their disease is well-managed -- there's this burden that's always in the back of their mind. The frequent infusions, the cost of treatment, the need to plan for infusions when traveling, what happens if they do experience a bleed, and so on, is always there," Cuker said. "Now that we have patients who were treated on this study and are essentially cured of their hemophilia, they're telling us about realizing a new, 'hemophilia-free state of mind.' As a physician, it's amazing to see my patients so happy with their new reality."

The study was supported by Pfizer. Cuker has previously served as a paid consultant for Pfizer.