HEMGENIX Gene Therapy Shows Sustained Five-Year Efficacy in Hemophilia B Patients
核心洞察
Five-year data from the Phase 3 HOPE-B trial published in the New England Journal of Medicine confirm HEMGENIX's durable efficacy, with 94% of patients remaining free from continuous prophylaxis treatment.
Mean factor IX activity levels remained strong at 36.1% at year five, while bleeding rates were reduced by approximately 90% compared to baseline prophylaxis treatment.
The gene therapy demonstrated a favorable safety profile with no serious treatment-related adverse events, reinforcing its potential as a transformative one-time treatment for adults with hemophilia B (搜索).
CSL (搜索) announced five-year results from the pivotal Phase 3 HOPE-B study demonstrating the sustained durability and safety of HEMGENIX (etranacogene dezaparvovec-drlb), a one-time gene therapy for adults with hemophilia B (搜索). The data, published in the New England Journal of Medicine and presented at the American Society of Hematology Annual Meeting, confirm the therapy's consistent long-term performance in delivering durable factor IX activity levels and sustained bleed protection.
Sustained Therapeutic Benefit Over Five Years
The study enrolled 54 adult male participants with severe or moderately severe hemophilia B (搜索), with 50 completing five years of follow-up. Results showed that 94% of patients (51 of 54) remained free from the burden of continuous prophylaxis treatment through five years following a single infusion of HEMGENIX, demonstrating sustained therapeutic benefit.
Mean factor IX activity levels remained consistently above 36% during years one through five post-infusion. Specifically, mean factor IX levels were 41.5 IU/dL at year one, 36.7 IU/dL at year two, 38.6 IU/dL at year three, 37.4 IU/dL at year four, and 36.1 IU/dL at year five.
Significant Reduction in Bleeding Episodes
The therapy demonstrated substantial bleed protection compared to baseline prophylaxis treatment. The mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from the lead-in period (4.16) compared to year five (0.40) post-infusion. Joint bleeds were reduced by 93% from lead-in (mean ABR of 2.34 to 0.16 at year five) and spontaneous bleeds were reduced by 94% (mean ABR of 1.52 during lead-in versus 0.09 during year five).
"The five-year HOPE-B results mark a pivotal milestone for gene therapy, providing clear, long-term data of the ability of HEMGENIX to potentially transform care for adults with hemophilia B (搜索)," said Steven Pipe, MD, Professor of Pediatrics and Pathology at the University of Michigan. "For those who have relied on frequent prophylactic infusions, achieving lasting bleed control from a single treatment offers the potential for greater day-to-day freedom and a life less burdened by the demands of ongoing therapy."
Favorable Safety Profile Maintained
HEMGENIX demonstrated a favorable safety profile over the five-year period. No serious adverse events were related to treatment with HEMGENIX. The therapy was generally well-tolerated, with a total of 100 treatment-related adverse events (TRAEs), most occurring in the first four months post-infusion. Only five TRAEs were reported between years four and five.
The most common adverse events were increases in alanine transaminase (ALT), for which nine participants (16.7%) received supportive care with reactive corticosteroids for a mean duration of 81.4 days. Two deaths occurred during the study due to non-treatment-related causes: one at approximately 15 months post-dose due to cardiogenic shock and urosepsis, and another at approximately 54 months post-dose due to cardiac amyloidosis.
Mechanism and Global Adoption
HEMGENIX uses an AAV5 (搜索) viral vector to deliver the Padua gene variant of Factor IX (FIX-Padua) to liver cells, generating factor IX proteins that are eight times more active than normal. The therapy enables the body to continuously produce factor IX, the deficient protein in hemophilia B (搜索), addressing the underlying cause of the bleeding disorder.
The treatment has received regulatory approval in multiple countries including the United States, Canada, the UK, Switzerland, Australia, Saudi Arabia, Taiwan, South Korea, Singapore, and Hong Kong. More than 75 individuals across eight countries have received HEMGENIX in real-world settings, reflecting growing global adoption.
Extended Follow-up and Future Monitoring
Although the five-year data mark the final analysis for the HOPE-B study, participants who consent will continue to be monitored in the IX-TEND extended follow-up study, which will track patients for up to 15 years post-treatment. CSL (搜索) has also established a post-marketing registry to generate additional long-term safety, efficacy and durability data.
"We are incredibly proud to share the five-year results from the HOPE-B study, which reinforce the lasting impact of HEMGENIX as a one-time treatment option for adults with hemophilia B (搜索)," said Deborah Long, MD, Senior Vice President and Head of Medical Affairs at CSL (搜索). "These results highlight the meaningful difference HEMGENIX can make—helping people experience fewer bleeds compared to prophylaxis treatment and freeing them from the burden of regular ongoing treatment."