The gene therapy uses an adeno-associated virus serotype 5 (AAV5) vector to carry the hyperactive factor IX Padua variant and is given once at 2 × 10¹³ genome copies/kg.
The HOPE-B trial enrolled adult men with severe or moderately severe hemophilia B, defined as a factor IX level at or below 2 IU/dL.
This post hoc analysis covered the end-of-study data and looked specifically at responders, the patients who expressed transgene-derived factor IX and were able to discontinue prophylaxis.
Exogenous factor IX use fell 98%.
The authors concluded that treatment with etranacogene dezaparvovec led to sustained endogenous factor IX activity at a nearly normal level, less frequent bleeding, and reduced use of factor IX during 5 years after infusion in responders.
Five years after a single infusion, most men treated with etranacogene dezaparvovec in the HOPE-B trial still had near-normal factor IX activity and few bleeds, according to a report by investigators at the International Society on Thrombosis and Haemostasis (ISTH) 2026 Congress in Paris, France.
The gene therapy uses an adeno-associated virus serotype 5 (AAV5) vector to carry the hyperactive factor IX Padua variant and is given once at 2 × 10¹³ genome copies/kg. The HOPE-B trial enrolled adult men with severe or moderately severe hemophilia B, defined as a factor IX level at or below 2 IU/dL. The trial met its primary end point years ago. This post hoc analysis covered the end-of-study data and looked specifically at responders, the patients who expressed transgene-derived factor IX and were able to discontinue prophylaxis.
Of the 54 men enrolled, 52 responded and 50 completed all 5 years of the study. Endogenous factor IX activity held steady over that span, from a mean level of 39.0 IU/dL at month 6 to a level of 36.1 IU/dL at year 5.
Bleeding rates fell and stayed down. Measured against each patient’s own lead-in period during prophylaxis, adjusted annualized bleeding rates over months 7 to 60 dropped 82% overall, from 3.99 to 0.71. Joint bleeds fell 90%, from 2.20 to 0.23. Reductions in factor IX–treated, spontaneous, and traumatic bleeds came to 87%, 86%, and 82%, respectively. All were significant at P<0.0001.
Exogenous factor IX use fell 98%. Responders used 262,077 IU a year during lead-in and 5,919 IU a year afterward.
Two patients did not respond. One had by far the highest baseline AAV5- neutralizing antibody titer in the cohort, 3,212.3. The other received only about 10% of the intended dose after an infusion-related reaction. Among responders, neutralizing antibody titers ranged from below 7 to 678. That range points to a practical question for clinicians weighing the therapy: how much preexisting AAV5 immunity is too much before a patient should be ruled out?
The effect was not permanent in every case. One responder returned to a regimen of continuous prophylaxis at about 29 months.
No serious treatment-related adverse events were reported across the 5 years, and there were no cases of oncogenicity or late hepatotoxicity. Two patients died, both from causes unrelated to treatment.
The authors concluded that treatment with etranacogene dezaparvovec led to sustained endogenous factor IX activity at a nearly normal level, less frequent bleeding, and reduced use of factor IX during 5 years after infusion in responders. They also note that the safety profile was favorable.
