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Promising Advances in Hemophilia B Treatment Through Gene Therapy
Recent findings from an international Phase III clinical trial indicate a substantial reduction in bleeding episodes among adults with hemophilia B following a single infusion of gene therapy. The study, published in the New England Journal of Medicine, was conducted by researchers at the University of Pennsylvania Perelman School of Medicine in collaboration with a multicenter team of investigators.
Hemophilia, a hereditary disorder, impairs the blood’s clotting ability, affecting approximately 30,000 individuals in the United States, predominantly males. If left untreated, hemophilia can lead to spontaneous bleeding episodes, especially into the joints, resulting in painful damage and mobility constraints over time. Hemophilia B specifically arises from insufficient levels of clotting factor IX, with the gene therapy designed to enable the liver to produce this crucial factor, thus facilitating proper blood clotting and reducing the risk of recurrent bleeds.
“Within days of receiving the gene therapy, many patients in the study began producing factor IX for the first time in their lives,” shared Dr. Adam Cuker, the study’s lead investigator and section chief for Hematology at the Penn Blood Disorders Center. “While we exercise caution with the term ‘cure,’ the impact on many patients has been transformative.”
After a minimum follow-up period of one year, the trial participants exhibited an average 71 percent decrease in bleeding rates when compared to the previous year, during which they were receiving routine prophylactic infusions of factor IX, the traditional treatment method. Notably, more than half of the 45 patients evaluated did not experience any bleeding episodes post-treatment.
FDA Approval and New Gene Therapy Options
In light of these encouraging results, the FDA granted approval for the gene therapy, known as fidanacogene elaparvovec, in April 2024. Dr. Cuker also served as the site lead for the clinical trial at Penn Medicine, which emerged as one of the leading enrollment sites. This therapy marks the second gene treatment authorized for hemophilia B, following the approval of etranacogene dezaparvovec-drlb in November 2022, with various medical centers across the U.S. offering both treatments.
It is important to note that gene therapies come with specific eligibility criteria and necessitate expert knowledge for patient selection, risk and benefit education, and post-treatment monitoring. Penn Medicine provides access to several clinical trials focused on gene therapies and possesses the expertise needed to administer FDA-approved treatments effectively.
In this trial, the most frequently observed adverse effect stemmed from an immune response targeting liver cells involved in the gene therapy process, which, if unchecked, could jeopardize the therapy’s effectiveness. Patients experiencing this reaction were treated with steroids to mitigate the immune response effects. Ongoing monitoring of these patients will continue for a minimum of five years to assess potential long-term side effects.
The Transformative Potential of Gene Therapy
Currently employed prophylactic treatments for hemophilia B, including regular factor IX infusions, are known to be effective but can be cumbersome for patients. Depending on the specific treatment regimen, individuals may require infusions as frequently as multiple times a week. Many patients become adept at self-administering these infusions at home. The aim of such preventative treatment is to maintain sufficient levels of factor IX in the bloodstream to avert bleeding, although episodes may still occur.
In contrast, the new gene therapy requires only a one-time dose, with the majority of study participants not needing to return to routine prophylactic treatments post-infusion. “Patients frequently express that, even with effective management, the ongoing burden of their condition lingers,” Dr. Cuker remarked. “With this new therapy, we are witnessing patients embracing what they describe as a ‘hemophilia-free state of mind.’ It’s truly rewarding as a physician to observe the joy it brings to my patients’ lives.”
The research was supported by Pfizer, and Dr. Cuker has previously consulted for the company.
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