Single Dose Gene Therapy Shows Promise in Reducing Bleeding Episodes in Haemophilia Patients

“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.”

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.

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.

The new gene therapy only requires a single dose in contrast to the standard therapy 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.”

Reference: Cuker, A., Kavakli, K., Frenzel, L., Wang, J.-D., Astermark, J., Cerqueira, M. H., Iorio, A., Katsarou-Fasouli, O., Klamroth, R., Shapiro, A. D., Hermans, C., Ishiguro, A., Leavitt, A. D., Oldenburg, J. B., Ozelo, M. C., Teitel, J., Biondo, F., Fang, A., Fuiman, J., McKay, J., Sun, P., Rasko, J. E. J., & Rupon, J. (2024). Gene therapy with fidanacogene elaparvovec in adults with hemophilia B. New England Journal of Medicine, 391(12), 1108-1118. https://doi.org/10.1056/NEJMoa2302982