Gene therapy using etranacogene dezaparvovec was associated with favorable safety and efficacy in a noninferiority analysis comparing this treatment with factor IX (FIX) prophylaxis in patients with hemophilia B. Study results were reported in the New England Journal of Medicine and were also presented at the 16th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD).

In the multicenter, open-label, single-dose, phase 3 HOPE-B trial ( Identifier: NCT03569891), patients with hemophilia B were treated with a single infusion of etranacogene dezaparvovec after a lead-in period of at least 6 months of receiving FIX prophylaxis. Etranacogene dezaparvovec contains an adeno-associated virus 5 (AAV5) vector with Padua FIX variant, and it was given at a dose of 2×1013 genome copies per kilogram of body weight in this study.

The annualized bleeding rate (ABR) was the primary study endpoint, which was examined in a noninferiority-based analysis of the ABR in months 7 through 18 after infusion in comparison with the ABR during the lead-in period. Other efficacy and safety endpoints were also evaluated.

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The study included 54 male patients with a mean age of 41.5 years, 81% of whom had severe hemophilia B at the time of diagnosis, whereas 19% had moderately severe hemophilia B. In the lead-in period, the ABR was 4.19 (95% CI, 3.22-5.45), while during months 7 through 18 postinfusion the ABR had dropped to 1.51 (95% CI, 0.81-2.82). The adjusted ABR ratio was 0.36 (95% CI, 0.20-0.64; P <.001) for the period of months 7 through 18 postinfusion, compared with lead-in. In addition to demonstrating noninferiority, superiority was also reported for the etranacogene dezaparvovec infusion compared with FIX prophylaxis.

Patients also showed increases from baseline in factor IX activity by a least-squares mean of 34.3 percentage points (95% CI, 29.5-39.1; P <.001) at 18 months after treatment. At 6 months postinfusion, there had been a least-squares mean increase in factor IX activity of 36.2 percentage points (95% CI, 31.4-41.0; P <.001) from baseline. There also was a mean reduction in usage of factor IX concentrate of 248,825 IU/year/participant during months 7 through 18 after treatment, compared with the lead-in period.

Adverse events (AEs) of any cause were reported in all patients. The most common any-cause AEs were arthralgia (33% of patients), headache (30%), nasopharyngitis (28%), and fatigue (26%). Serious AEs were reported in 24% of patients, but none of these were deemed to be related to treatment.

One death from cardiogenic shock occurred approximately 15 months after infusion, but this was considered unrelated to treatment. Infusion-related AEs of special interest were reported in 13% of patients. Pre-existing AAV5 neutralizing antibodies did not appear to influence AEs.

“In our study, etranacogene dezaparvovec had a favorable safety and efficacy profile in men with severe or moderately severe hemophilia B, including those with preexisting AAV5 neutralizing antibodies,” the study investigators concluded in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Pipe SW, Leebeek FWG, Recht M, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 2023;388(8):706-718. doi:10.1056/NEJMoa2211644