Single-dose gene therapy could change lives of adults with hemophilia B

Adults with hemophilia B saw their number of bleeding episodes reduced by an average of 71% after a single infusion of gene therapy, according to results of an international phase III clinical trial published in the journal New England Journal of Medicine by researchers from the Perelman School of Medicine at the University of Pennsylvania and a multicenter group of researchers.

Hemophilia is a genetic disorder that limits the blood’s ability to clot and affects about 30,000 people in the United States, mostly men. If left untreated, it can cause spontaneous bleeding, especially internal bleeding into 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 allows the liver to create factor IX, which helps the blood clot and protects patients from frequent bleeding.

“What we saw in the patients in this study was that within days of receiving the gene therapy infusion, it took hold and their bodies began producing factor IX for the first time in their lives,” said study investigator and senior author Adam Cuker, MD, MS, 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 when we use the word ‘cure,’ especially until we have longer follow-up data, but for many of these patients it has been life-changing.”

After at least one year of follow-up, study participants experienced an average 71% reduction in bleeding rates after receiving 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 gene therapy.

FDA Approved Gene Therapies

Based on the results of this study, the FDA approved the gene therapy (fidanacogene elaparvovec) in April 2024. Cuker was the clinical trial site lead at Penn Medicine, which was one of the primary enrolling sites for the study. This is the second form of gene therapy approved to treat hemophilia B.

The first such therapy (etranacogen 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 are subject to very specific guidelines that determine eligibility and require specialized knowledge to screen and select patients, provide information on the risks and benefits of treatment, and conduct post-treatment 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 side effect was related to an immune system attack on the liver cells targeted by the gene therapy, which can make the gene therapy ineffective if not treated promptly. In the study, affected patients were treated with steroids to limit this immune response. Patients in the study will continue to be followed for at least five years to monitor for potential long-term side effects.

A life-changing impact

In patients with haemophilia B, the current standard of care, which consists of continuous prophylactic infusions of factor IX, is generally effective but cumbersome. Depending on the specific product, a patient may need regular infusions, ranging from once every two weeks to several times a week. Most patients learn to set up their own intravenous infusions so that they can perform their infusions at home.

The goal of this prophylactic treatment is to regularly give the body enough factor IX to prevent bleeding, even if it still occurs. In contrast, the new gene therapy requires only one dose, and most patients in the study did not need to repeat prophylactic factor IX treatments.

“People born with hemophilia tell us that even though their disease is well managed, the burden is always on their minds. The frequent infusions, the cost of treatment, having to plan for infusions when traveling, what happens if there is a bleed, etc., are always there,” Cuker said.

“Now that we have patients who have been treated in this study and are virtually cured of their hemophilia, they tell us that they have reached a new state of mind, that of ‘freeing hemophilia.’ As a physician, it is incredible to see my patients so happy with their new reality.”