Hemophilia B: Gene Therapy Shows Promise

TOPLINE:

Fidanacogene elaparvovec gene therapy reduced the annualized bleeding rate by 71% in patients with hemophilia B. Factor IX activity levels were sustained at 26.9% at 15 months post-treatment.

METHODOLOGY:

• A phase 3 open-label study was conducted involving 45 men aged 18-65 years with hemophilia B and a factor IX level ≤ 2%.
• Participants received a single intravenous infusion of fidanacogene elaparvovec at a dose of 5 × 10¹¹ vector genome copies per kilogram.
• The primary endpoint was the annualized bleeding rate from week 12 to month 15 post-treatment compared with the prophylaxis lead-in period.
• Secondary endpoints included the annualized rate of treated bleeding episodes, factor IX activity levels, and safety assessments.
• The study was conducted at 27 centers in 13 countries, with follow-up data collected for up to 15 months.

TAKEAWAY:

• The annualized bleeding rate decreased by 71% (annualized bleeding rate, 4.42 to 1.28 episodes per year) post-gene therapy (P = .008).
• Factor IX activity levels were sustained at a mean of 26.9% (factor IX activity levels, 1.9%-119.0%) at 15 months post-treatment.
• No serious adverse events related to the infusion, thrombotic events, or development of factor IX inhibitors were observed.
• A total of 28 participants (62%) received glucocorticoids for increased aminotransferase levels or decreased factor IX levels.

IN PRACTICE:

“Fidanacogene elaparvovec was superior to prophylaxis for the treatment of participants with hemophilia B, leading to reduced bleeding and stable factor IX expression,” the authors of the study wrote.

SOURCE:

This study was led by Adam Cuker, MD, University of Pennsylvania in Philadelphia. It was published online on September 26, 2024, in The New England Journal of Medicine.

LIMITATIONS:

This study’s limitations included the small sample size of 45 participants, which may have affected the generalizability of the findings. The follow-up period of 15 months may not have been sufficient to assess long-term safety and efficacy. The presence of anti–adeno-associated virus neutralizing antibodies in a significant portion of the screened population (59.5%) limited the eligible participants.

DISCLOSURES:

This study was supported by Pfizer. Cuker disclosed receiving grants from Pfizer. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.