Five-year results highlight new treatment option for hemophilia B
Gene therapy helped reduce bleeding and lower the need for infusions
- Five-year results suggest Hemgenix may help reduce bleeding in hemophilia B.
- Many patients needed far fewer factor IX infusions after treatment.
- Most maintained stable factor IX levels, with generally favorable safety.
After five years of follow-up, Hemgenix (etranacogene dezaparvovec-drlb) was associated with durable factor IX (FIX) levels, lower bleeding rates, and a substantial reduction in the need for regular FIX infusions, with a generally favorable long-term safety profile in men with severe or moderately severe hemophilia B.
These data come from the final analysis of HOPE-B (NCT03569891), an open-label Phase 3 clinical trial that supported the approval of Hemgenix as the first gene therapy for hemophilia B, a genetic condition caused by changes in the F9 gene that affect the FIX clotting protein.
The study, “Final Analysis of a Study of Etranacogene Dezaparvovec for Hemophilia B,” was published in The New England Journal of Medicine. It was funded by uniQure and CSL Behring, which acquired Hemgenix from uniQure and now markets it globally.
Understanding hemophilia B and how gene therapy works
In hemophilia B, the blood cannot clot properly to stop bleeding because FIX is faulty or missing. As a result, people may experience heavy bleeding or bleeding that lasts longer than usual and may still have breakthrough bleeding episodes even while receiving FIX replacement therapy.
Hemgenix delivers a working copy of the F9 gene to liver cells using a harmless viral vector called AAV5. It is given as an intravenous (into-the-vein) infusion and travels to the liver, where cells use the new gene to produce FIX. This raises FIX levels in the blood and helps prevent and control bleeding.
Its approval in the U.S. and other countries was based on the primary analysis of HOPE-B, which included data from the first 18 months of the study. Of the 54 men who received a single dose of Hemgenix as part of this clinical trial — including 53 who received the full planned dose — most (82%) had severe hemophilia B, and 50 (93%) completed five years of follow-up.
Before receiving Hemgenix, the participants went through a lead-in period of at least six months. During this time, they received regular preventive FIX infusions to measure their usual bleeding rate. Afterward, each person received a single intravenous infusion of the gene therapy.
The main outcomes measured over five years included bleeding frequency, FIX levels produced by the body, and side effects. Bleeding frequency was reported as the annualized bleeding rate, which estimates the number of bleeding episodes that occur in one year.
Study results show fewer bleeding episodes over five years
Before gene therapy, the average annualized bleeding rate was 4.16. Consistent with earlier data from the first 18 months of the study, the rate from months 7 to 60 after receiving Hemgenix was 1.52, representing a 63% reduction in bleeding episodes.
The production of FIX in the liver, known as endogenous FIX expression, remained stable over time. All but two participants (96%) had endogenous FIX expression and “were considered to have had a response,” the researchers wrote. As a result, the average annual use of FIX infusions decreased by 96%.
Some participants had antibodies against the virus used to deliver the gene therapy, called AAV5 neutralizing antibodies. These antibodies can sometimes reduce the effectiveness of gene therapy. However, in this study, Hemgenix appeared to work similarly well regardless of whether participants had these antibodies at the start.
Side effects that were possibly related to Hemgenix were uncommon after the first six months and were generally low grade. Overall, a single infusion of the gene therapy was associated with long-lasting endogenous FIX expression and low bleeding rates over five years, supporting its potential long-term benefit.
To learn more about long-term safety and effectiveness, participants in the HOPE-B clinical trial who give consent will be followed for up to 15 years in the IX-TEND 3003 extension study (NCT05962398), the researchers noted.
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