# Etranacogene dezaparvovec in people with hemophilia B and without adeno-associated virus serotype 5 neutralizing antibodies: a 4-year subgroup analysis of the Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) trial

## TL;DR

A gene therapy called etranacogene dezaparvovec significantly reduced bleeding in hemophilia B patients without specific antibodies for four years.

## Contribution

A 4-year post hoc analysis of NAb− hemophilia B patients treated with etranacogene dezaparvovec, showing sustained efficacy and safety.

## Key findings

- Bleeding rates dropped significantly over four years post-treatment compared to the lead-in period.
- Endogenous FIX activity remained stable at four years, with minimal need for exogenous FIX.
- No treatment-related oncogenic events or persistent hepatotoxicity were observed.

## Abstract

In the phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) trial, a single dose of etranacogene dezaparvovec was administered to people with severe or moderately severe hemophilia B following a lead-in period (≥6 months) during which they received factor (F)IX prophylaxis. Participants were enrolled regardless of adeno-associated virus serotype 5 (AAV5)-neutralizing antibody (NAb) status at screening.

To determine efficacy, pharmacokinetic, and safety outcomes over 4 years postgene therapy in HOPE-B participants who were NAb-negative (NAb−).

Participants provided serum samples for AAV5 NAb determination using an in vitro AAV5 transduction inhibition assay prior to etranacogene dezaparvovec infusion. Participants who were AAV5 NAb− at this time point were examined in the post hoc subgroup analysis.

In NAb− participants (N = 33), the mean adjusted annualized bleeding rate was significantly reduced between months 7 and 48 postetranacogene dezaparvovec vs lead-in (0.57 vs 3.80; P < .0001). In years 1 to 4, the annualized bleeding rates were 0.99, 0.72, 0.41, and 0.41, respectively (P < .0001 vs lead-in; N = 33 throughout). The mean (SD) endogenous FIX activity was 40.6 IU/dL (18.6) at month 6 postinfusion (N = 33), remained stable, and was 39.0 IU/dL (16.8) at year 4 (N = 33). Exogenous FIX consumption decreased by 99% during months 7 to 48 vs the lead-in period, and no NAb− participant returned to continuous FIX prophylaxis for 4 years postinfusion. No treatment-related oncogenic events or persistent late hepatotoxicity were observed.

Etranacogene dezaparvovec proved to be highly effective, superior to FIX prophylaxis for bleeding protection, and safe for 4 years postinfusion in NAb− persons with severe or moderately severe hemophilia B.

•HOPE-B tested etranacogene dezaparvovec in people with hemophilia B with or without vector antibodies.•This post hoc study reports 4-year results postgene therapy in antibody-negative patients.•Etranacogene dezaparvovec was safe and reduced bleeding events compared with standard therapy.•Around half of the patients produced stable FIX levels comparable to those of people without hemophilia.

HOPE-B tested etranacogene dezaparvovec in people with hemophilia B with or without vector antibodies.

This post hoc study reports 4-year results postgene therapy in antibody-negative patients.

Etranacogene dezaparvovec was safe and reduced bleeding events compared with standard therapy.

Around half of the patients produced stable FIX levels comparable to those of people without hemophilia.