Hemgenix Gene Therapy Shows Sustained Benefits Over 5 Years in Hemophilia B: NEJM
USA: Final HOPE-B trial results published in The New England Journal of Medicine have revealed that patients with hemophilia B maintained low bleeding rates and stable endogenous factor IX levels for five years following a single infusion of etranacogene dezaparvovec (Hemgenix). The adjusted annualized bleeding rate (ABR) decreased from 4.16 during the lead-in period to 1.52 between months 7 and 60 post-treatment, representing a 63% reduction.
Hemophilia B, a genetic bleeding disorder caused by deficient factor IX activity, has traditionally required lifelong prophylactic intravenous infusions. Etranacogene dezaparvovec, a gene therapy comprising an adeno-associated virus serotype 5 (AAV5) vector and the highly active Padua variant of factor IX, aims to provide a durable, single-dose solution that restores endogenous factor IX production and reduces bleeding episodes. Initial analyses had already demonstrated reductions in bleeding rates and low-grade adverse events; the final five-year data now confirm the long-term benefits and safety of this approach.
The HOPE-B trial enrolled adult men with severe hemophilia B (factor IX activity ≤2 IU/dL) who completed a lead-in period of at least six months on standard factor IX prophylaxis. Participants received a single intravenous infusion of etranacogene dezaparvovec regardless of preexisting neutralizing antibodies to AAV5. Over the five-year follow-up, researchers monitored annualized bleeding rates, factor IX activity, and safety outcomes.
The findings were as follows:
- Among 54 participants, the mean annualized bleeding rate decreased from 4.16 during the lead-in period to 1.52 during months 7–60 after infusion, a 63% reduction.
- Endogenous factor IX levels remained stable over five years, with a mean activity of 36.1 ± 15.7 IU/dL at year five.
- Annual factor IX use for prophylaxis and bleeding treatment dropped by 96%, from 257,339 IU per year before therapy to 10,924 IU per year post-treatment.
- Treatment efficacy was comparable in patients with or without preexisting AAV5 neutralizing antibodies, suggesting baseline immunity did not impact outcomes.
- Adverse events possibly related to therapy were rare after the first six months, with no new safety concerns observed during long-term follow-up.
The five-year data from the HOPE-B trial highlight the potential of etranacogene dezaparvovec to transform hemophilia B management. A single infusion can provide durable factor IX expression, substantially reduce bleeding episodes, and minimize reliance on regular factor replacement therapy. These findings underscore the promise of gene therapy as a long-term, effective treatment option for patients with hemophilia B.
"While these results are encouraging, ongoing monitoring and larger post-marketing studies will be essential to further assess long-term safety, durability of response, and the therapy’s impact on quality of life. Nonetheless, the HOPE-B trial provides compelling evidence that etranacogene dezaparvovec may redefine standard care for hemophilia B patients worldwide," the authors concluded.
Reference:
DOI: 10.1056/NEJMoa2514332
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