Data from the pivotal HOPE-B study demonstrates that Hemgenix (etranacogene dezaparvovec-drlb) continues to show sustained efficacy and safety in adults with hemophilia B four years after a one-time infusion. The findings, presented at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), highlight the potential for long-term bleed protection and improved quality of life for patients. Hemgenix, developed by CSL Behring in collaboration with uniQure, has already been approved by the FDA and other regulatory bodies.
Sustained Factor IX Activity and Reduced Bleeding
The Phase 3 HOPE-B trial (NCT03569891) enrolled 54 adult male participants with severe or moderately severe hemophilia B. The results showed that Hemgenix produced mean factor IX levels of 41.5 IU/dL at year one, which were sustained at 37.4 IU/dL at year four post-infusion. This sustained activity led to a significant reduction in bleeding events. The mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in (4.16) to year four (0.40).
Elimination of Prophylaxis and Improved Joint Health
One of the most significant outcomes of the study was the elimination of continuous prophylaxis treatment in the majority of patients. At year four, 94% of patients remained free of continuous prophylaxis. Joint bleeds, a major burden for hemophilia B patients, were also significantly reduced, from a mean ABR of 2.34 at lead-in to 0.09 during year four.
Safety Profile and Adverse Events
HEMGENIX was generally well-tolerated, with no serious adverse events related to treatment. A total of 96 treatment-related adverse events (AEs) were reported, with 92 (96%) occurring in the first six months post-treatment. The most common adverse event was an increase in alanine transaminase (ALT), which was managed with supportive care using corticosteroids for a mean duration of 81.4 days.
Expert Commentary
"Hemophilia B can cause spontaneous bleeds into the joints, resulting in extreme pain and progressive, arthritis-like damage, which can lead to permanent physical debility," said Steven Pipe, MD, professor of pediatrics and pathology and director of the Hemophilia and Coagulation Disorders Program at the University of Michigan. "These results underscore the ability of [etranacogene dezaparvovec-drlb] to offer long-term bleed protection with a one-time treatment, resulting in dramatic decreases in all ABRs, including joint bleeds, and sustained independence from regular prophylactic infusions."
Implications for Hemophilia B Treatment
The four-year data from the HOPE-B trial reinforce the potential of Hemgenix as a transformative treatment for hemophilia B. By providing sustained factor IX activity and reducing bleeding rates, Hemgenix offers patients the possibility of a life free from regular prophylactic infusions. The ongoing post-marketing registry established by CSL Behring will continue to monitor the long-term safety, efficacy, and durability of the gene therapy.
