Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial

Robert Klamroth; Paul E Monahan; Paul Van der Valk; Doris Quon; Rashid Saeed Kazmi; Michiel Coppens; Niamh O'Connell; Steven W Pipe; Annette von Drygalski; Saira Afzal; Richard Gabriel; Loubna Youssar; Sean Gill; Nathalie Jansen; Fei Wang; Sandra Le Quellec; Cedric Hermans

doi:10.1016/j.rpth.2026.103360

Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial

Robert Klamroth
, Paul E Monahan
, Paul Van der Valk
, Doris Quon
, Rashid Saeed Kazmi
, Michiel Coppens
, Niamh O'Connell
, Steven W Pipe
, Annette von Drygalski
, Saira Afzal
, Richard Gabriel
, Loubna Youssar
, Sean Gill
, Nathalie Jansen
, Fei Wang
, Sandra Le Quellec^*
, Cedric Hermans

^*Corresponding author for this work

Hematology/Van Creveldclinic

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) is the first phase 3 trial of adeno-associated virus (AAV) serotype 5 vector-based gene therapy for hemophilia B to have enrolled participants with neutralizing antibodies (NAbs) to the viral vector.

OBJECTIVES: Evaluate the efficacy and safety of etranacogene dezaparvovec in a post hoc subgroup of participants with preexisting AAV5 NAbs 4 years posttherapy.

METHODS: After a ≥6-month lead-in period on continuous prophylaxis, people with moderately severe/severe hemophilia B (factor [F]IX ≤ 2%) received a single infusion of etranacogene dezaparvovec. AAV5 NAb status prior to infusion was determined. FIX activity, annualized bleeding rates (ABRs), and safety were evaluated in participants with preexisting AAV5 NAbs.

RESULTS: A total of 21/54 participants had detectable preexisting AAV5 NAbs (titer: 8.5-678, n = 20; titer: 3212, n = 1). Two participants did not respond to treatment (high titer: 3212, n = 1; received partial dose, n = 1). The mean FIX activity was 36 IU/dL (SD, 18) at 1 year ( n = 18) and 34 IU/dL (SD, 16) at 4 years ( n = 15) posttreatment. Unadjusted ABRs for all bleeds (treated and untreated) decreased by 74.4% from 4.64 during lead-in to 1.18 during months 7 to 48 ( n = 21). ABRs for spontaneous and joint bleeds decreased by 79% and 82%, respectively. The mean FIX consumption decreased from 245,476 IU/y (SD, 144,497) during lead-in to 23,975 IU/y (SD, 48.928) during years 1 to 4 ( P < .0001). The most frequent treatment-related adverse events were infusion-related reactions (23.8%) and transient alanine aminotransferase elevations (14.3%). No late hepatotoxicity was observed.

CONCLUSION: Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population.

Original language	English
Article number	103360
Number of pages	1
Journal	Research and practice in thrombosis and haemostasis
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.rpth.2026.103360
Publication status	Published - Jan 2026

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Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trialFinal published version, 2.47 MBLicence: CC BY

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Klamroth, R., Monahan, P. E., Van der Valk, P., Quon, D., Kazmi, R. S., Coppens, M., O'Connell, N., Pipe, S. W., von Drygalski, A., Afzal, S., Gabriel, R., Youssar, L., Gill, S., Jansen, N., Wang, F., Le Quellec, S., & Hermans, C. (2026). Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial. Research and practice in thrombosis and haemostasis, 10(1), Article 103360. https://doi.org/10.1016/j.rpth.2026.103360

@article{a41aaad5370f45f1a9bc8a61d71e5f6b,

title = "Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial",

abstract = "BACKGROUND: Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) is the first phase 3 trial of adeno-associated virus (AAV) serotype 5 vector-based gene therapy for hemophilia B to have enrolled participants with neutralizing antibodies (NAbs) to the viral vector.OBJECTIVES: Evaluate the efficacy and safety of etranacogene dezaparvovec in a post hoc subgroup of participants with preexisting AAV5 NAbs 4 years posttherapy.METHODS: After a ≥6-month lead-in period on continuous prophylaxis, people with moderately severe/severe hemophilia B (factor [F]IX ≤ 2\%) received a single infusion of etranacogene dezaparvovec. AAV5 NAb status prior to infusion was determined. FIX activity, annualized bleeding rates (ABRs), and safety were evaluated in participants with preexisting AAV5 NAbs.RESULTS: A total of 21/54 participants had detectable preexisting AAV5 NAbs (titer: 8.5-678, n = 20; titer: 3212, n = 1). Two participants did not respond to treatment (high titer: 3212, n = 1; received partial dose, n = 1). The mean FIX activity was 36 IU/dL (SD, 18) at 1 year ( n = 18) and 34 IU/dL (SD, 16) at 4 years ( n = 15) posttreatment. Unadjusted ABRs for all bleeds (treated and untreated) decreased by 74.4\% from 4.64 during lead-in to 1.18 during months 7 to 48 ( n = 21). ABRs for spontaneous and joint bleeds decreased by 79\% and 82\%, respectively. The mean FIX consumption decreased from 245,476 IU/y (SD, 144,497) during lead-in to 23,975 IU/y (SD, 48.928) during years 1 to 4 ( P < .0001). The most frequent treatment-related adverse events were infusion-related reactions (23.8\%) and transient alanine aminotransferase elevations (14.3\%). No late hepatotoxicity was observed. CONCLUSION: Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population.",

author = "Robert Klamroth and Monahan, \{Paul E\} and \{Van der Valk\}, Paul and Doris Quon and Kazmi, \{Rashid Saeed\} and Michiel Coppens and Niamh O'Connell and Pipe, \{Steven W\} and \{von Drygalski\}, Annette and Saira Afzal and Richard Gabriel and Loubna Youssar and Sean Gill and Nathalie Jansen and Fei Wang and \{Le Quellec\}, Sandra and Cedric Hermans",

note = "{\textcopyright} 2026 The Author(s).",

year = "2026",

month = jan,

doi = "10.1016/j.rpth.2026.103360",

language = "English",

volume = "10",

journal = "Research and practice in thrombosis and haemostasis",

issn = "2475-0379",

publisher = "Elsevier",

number = "1",

}

Klamroth, R, Monahan, PE, Van der Valk, P, Quon, D, Kazmi, RS, Coppens, M, O'Connell, N, Pipe, SW, von Drygalski, A, Afzal, S, Gabriel, R, Youssar, L, Gill, S, Jansen, N, Wang, F, Le Quellec, S & Hermans, C 2026, 'Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial', Research and practice in thrombosis and haemostasis, vol. 10, no. 1, 103360. https://doi.org/10.1016/j.rpth.2026.103360

Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial. / Klamroth, Robert; Monahan, Paul E; Van der Valk, Paul et al.
In: Research and practice in thrombosis and haemostasis, Vol. 10, No. 1, 103360, 01.2026.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies

T2 - 4-year subgroup results from the HOPE-B trial

AU - Klamroth, Robert

AU - Monahan, Paul E

AU - Van der Valk, Paul

AU - Quon, Doris

AU - Kazmi, Rashid Saeed

AU - Coppens, Michiel

AU - O'Connell, Niamh

AU - Pipe, Steven W

AU - von Drygalski, Annette

AU - Afzal, Saira

AU - Gabriel, Richard

AU - Youssar, Loubna

AU - Gill, Sean

AU - Jansen, Nathalie

AU - Wang, Fei

AU - Le Quellec, Sandra

AU - Hermans, Cedric

PY - 2026/1

Y1 - 2026/1

N2 - BACKGROUND: Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) is the first phase 3 trial of adeno-associated virus (AAV) serotype 5 vector-based gene therapy for hemophilia B to have enrolled participants with neutralizing antibodies (NAbs) to the viral vector.OBJECTIVES: Evaluate the efficacy and safety of etranacogene dezaparvovec in a post hoc subgroup of participants with preexisting AAV5 NAbs 4 years posttherapy.METHODS: After a ≥6-month lead-in period on continuous prophylaxis, people with moderately severe/severe hemophilia B (factor [F]IX ≤ 2%) received a single infusion of etranacogene dezaparvovec. AAV5 NAb status prior to infusion was determined. FIX activity, annualized bleeding rates (ABRs), and safety were evaluated in participants with preexisting AAV5 NAbs.RESULTS: A total of 21/54 participants had detectable preexisting AAV5 NAbs (titer: 8.5-678, n = 20; titer: 3212, n = 1). Two participants did not respond to treatment (high titer: 3212, n = 1; received partial dose, n = 1). The mean FIX activity was 36 IU/dL (SD, 18) at 1 year ( n = 18) and 34 IU/dL (SD, 16) at 4 years ( n = 15) posttreatment. Unadjusted ABRs for all bleeds (treated and untreated) decreased by 74.4% from 4.64 during lead-in to 1.18 during months 7 to 48 ( n = 21). ABRs for spontaneous and joint bleeds decreased by 79% and 82%, respectively. The mean FIX consumption decreased from 245,476 IU/y (SD, 144,497) during lead-in to 23,975 IU/y (SD, 48.928) during years 1 to 4 ( P < .0001). The most frequent treatment-related adverse events were infusion-related reactions (23.8%) and transient alanine aminotransferase elevations (14.3%). No late hepatotoxicity was observed. CONCLUSION: Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population.

AB - BACKGROUND: Health Outcomes with Padua Gene; Evaluation in Hemophilia B (HOPE-B) is the first phase 3 trial of adeno-associated virus (AAV) serotype 5 vector-based gene therapy for hemophilia B to have enrolled participants with neutralizing antibodies (NAbs) to the viral vector.OBJECTIVES: Evaluate the efficacy and safety of etranacogene dezaparvovec in a post hoc subgroup of participants with preexisting AAV5 NAbs 4 years posttherapy.METHODS: After a ≥6-month lead-in period on continuous prophylaxis, people with moderately severe/severe hemophilia B (factor [F]IX ≤ 2%) received a single infusion of etranacogene dezaparvovec. AAV5 NAb status prior to infusion was determined. FIX activity, annualized bleeding rates (ABRs), and safety were evaluated in participants with preexisting AAV5 NAbs.RESULTS: A total of 21/54 participants had detectable preexisting AAV5 NAbs (titer: 8.5-678, n = 20; titer: 3212, n = 1). Two participants did not respond to treatment (high titer: 3212, n = 1; received partial dose, n = 1). The mean FIX activity was 36 IU/dL (SD, 18) at 1 year ( n = 18) and 34 IU/dL (SD, 16) at 4 years ( n = 15) posttreatment. Unadjusted ABRs for all bleeds (treated and untreated) decreased by 74.4% from 4.64 during lead-in to 1.18 during months 7 to 48 ( n = 21). ABRs for spontaneous and joint bleeds decreased by 79% and 82%, respectively. The mean FIX consumption decreased from 245,476 IU/y (SD, 144,497) during lead-in to 23,975 IU/y (SD, 48.928) during years 1 to 4 ( P < .0001). The most frequent treatment-related adverse events were infusion-related reactions (23.8%) and transient alanine aminotransferase elevations (14.3%). No late hepatotoxicity was observed. CONCLUSION: Etranacogene dezaparvovec demonstrated long-term efficacy and safety in individuals with preexisting AAV5 NAb titers ≤ 678, expanding eligibility for gene therapy to a broader hemophilia B population.

U2 - 10.1016/j.rpth.2026.103360

DO - 10.1016/j.rpth.2026.103360

M3 - Article

C2 - 41756540

SN - 2475-0379

VL - 10

JO - Research and practice in thrombosis and haemostasis

JF - Research and practice in thrombosis and haemostasis

IS - 1

M1 - 103360

ER -

Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial

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