Adults with hemophilia B saw their number of bleeding episodes decrease by an average of 71 percent after a single infusion of gene therapy, according to results of an international phase III clinical trial published today in the New England Journal of Medicine by researchers at the Perelman School of Medicine at the University of Pennsylvania and a multicenter group of researchers.
Hemophilia is a genetic disorder that limits the ability of blood to clot and affects about 30,000 people in the United States, mostly men. If left untreated, it can lead to spontaneous bleeding, particularly internal bleeding in the joints, which over time can lead to painful joint damage and mobility problems. Hemophilia B is caused by a lack of clotting factor IX. Gene therapy enables the liver to create factor IX, which allows blood to clot and protects patients from frequent bleeding.
“What we saw in the patients in this study was that within a few days of receiving the gene therapy infusion, their disease took hold and their bodies began producing factor IX for the first time in their lives,” said senior author and investigator Dr. Adam Cuker, section chief of 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, study participants had an average 71 percent reduction in their bleeding rate after receiving the gene therapy, compared with the previous year, 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 had no bleeding after receiving the 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 leader for the clinical trial at Penn Medicine, which was one of the largest 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 determining eligibility and require specialized expertise to perform patient evaluation and selection, education about the risks and benefits of treatment, and post-therapy follow-up. Penn Medicine offers access to numerous gene therapy clinical trials 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 the liver cells targeted by the gene therapy, which can render the gene therapy ineffective if not treated promptly. In the study, affected patients were treated with steroids to limit this immune reaction. Patients in the study will continue to be monitored for at least five years to monitor for possible long-term side effects.
Life-changing impact
For patients with hemophilia B, the current standard treatment of continuous prophylactic factor IX infusions is generally effective but cumbersome. Depending on the specific product, a patient may require regular infusions from once every two weeks to several times a week. Most patients learn to place their own IV so they can complete their infusions at home. The goal of this prophylactic treatment is to regularly deliver enough factor IX to the body to prevent bleeding, even though it may still occur. In contrast, the new gene therapy requires only a single dose, and most patients in the study did not need to resume prophylactic factor IX treatments.
“We hear from people who were born with hemophilia that even if their disease is well controlled, they always have this burden on their mind. Frequent infusions, the cost of treatment, the need to plan for infusions when they travel, what happens if they bleed, etc. — it’s all there,” Cuker said. “Now that we have patients who were treated in this study and are essentially cured of their hemophilia, they tell us they’ve reached 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 previously worked as a paid consultant for Pfizer.