Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors

Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and...

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Autores: Shapiro, Amy D., Angchaisuksiri, Pantep, Astermark, Jan, Benson, Gary, Castaman, Giancarlo, Eichler, Hermann, Jiménez Yuste, Víctor Manuel, Kavakli, Kaan, Matsushita, Tadashi, Poulsen, Lone Hvitfeldt, Wheeler, Allison P., Young, Guy, Zupančić-Šalek, Silva, Oldenburg, Johannes, Chowdary, Pratima
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/707460
Acesso em linha:http://hdl.handle.net/10486/707460
https://dx.doi.org/10.1182/bloodadvances.2021006403
Access Level:Acceso aberto
Palavra-chave:concizumabconcizumab
Hemophilia A
Hemophilia A/B
Medicina
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spelling Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitorsShapiro, Amy D.Angchaisuksiri, PantepAstermark, JanBenson, GaryCastaman, GiancarloEichler, HermannJiménez Yuste, Víctor ManuelKavakli, KaanMatsushita, TadashiPoulsen, Lone HvitfeldtWheeler, Allison P.Young, GuyZupančić-Šalek, SilvaOldenburg, JohannesChowdary, PratimaconcizumabconcizumabHemophilia AHemophilia A/BMedicinaDespite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy. Both trials included main ($24 weeks) and extension (52-102 weeks) parts, with patients receiving concizumab 0.15 mg/kg with potential dose escalation to concizumab 0.20 or 0.25 mg/kg if they experienced $3 treated spontaneous bleeding episodes within 12 weeks. Endpoints included annualized bleeding rate (ABR), adverse events (AEs), and occurrence of antidrug antibodies. Thromboembolic events were AEs of special interest. Thirty-six patients with HA, 15 with HAwI, and 10 with HBwI were exposed to concizumab. Estimated ABRs during the main 1 extension parts at last dose level were 4.8 (95% confidence interval [CI], 3.2-7.2) and 6.4 (95% CI, 4.1-9.9) in explorer4 and explorer5, respectively (spontaneous ABRs were 1.8 [95% CI, 1.2-2.6] and 2.1 [95% CI, 1.3-3.3]). Most AEs were mild, with no deaths, events leading to withdrawal, or thromboembolic events. Anti-drug antibodies developed in 25% of patients and were low titer and transient, with no observed clinical effect in most cases. Results of the main 1 extension parts of these trials were consistent with results of the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypesThese studies were funded by Novo Nordisk A/S. Medical writing support, under the direction of the authors, was provided by Ashfield MedComms GmbH (an Ashfield Health company) and was funded by Novo Nordisk A/SAmerican Society of HematologyDepartamento de MedicinaFacultad de Medicina20222022-06-14research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/707460https://dx.doi.org/10.1182/bloodadvances.2021006403reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7074602026-06-23T12:46:27Z
dc.title.none.fl_str_mv Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
title Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
spellingShingle Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
Shapiro, Amy D.
concizumabconcizumab
Hemophilia A
Hemophilia A/B
Medicina
title_short Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
title_full Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
title_fullStr Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
title_full_unstemmed Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
title_sort Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
dc.creator.none.fl_str_mv Shapiro, Amy D.
Angchaisuksiri, Pantep
Astermark, Jan
Benson, Gary
Castaman, Giancarlo
Eichler, Hermann
Jiménez Yuste, Víctor Manuel
Kavakli, Kaan
Matsushita, Tadashi
Poulsen, Lone Hvitfeldt
Wheeler, Allison P.
Young, Guy
Zupančić-Šalek, Silva
Oldenburg, Johannes
Chowdary, Pratima
author Shapiro, Amy D.
author_facet Shapiro, Amy D.
Angchaisuksiri, Pantep
Astermark, Jan
Benson, Gary
Castaman, Giancarlo
Eichler, Hermann
Jiménez Yuste, Víctor Manuel
Kavakli, Kaan
Matsushita, Tadashi
Poulsen, Lone Hvitfeldt
Wheeler, Allison P.
Young, Guy
Zupančić-Šalek, Silva
Oldenburg, Johannes
Chowdary, Pratima
author_role author
author2 Angchaisuksiri, Pantep
Astermark, Jan
Benson, Gary
Castaman, Giancarlo
Eichler, Hermann
Jiménez Yuste, Víctor Manuel
Kavakli, Kaan
Matsushita, Tadashi
Poulsen, Lone Hvitfeldt
Wheeler, Allison P.
Young, Guy
Zupančić-Šalek, Silva
Oldenburg, Johannes
Chowdary, Pratima
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv concizumabconcizumab
Hemophilia A
Hemophilia A/B
Medicina
topic concizumabconcizumab
Hemophilia A
Hemophilia A/B
Medicina
description Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy. Both trials included main ($24 weeks) and extension (52-102 weeks) parts, with patients receiving concizumab 0.15 mg/kg with potential dose escalation to concizumab 0.20 or 0.25 mg/kg if they experienced $3 treated spontaneous bleeding episodes within 12 weeks. Endpoints included annualized bleeding rate (ABR), adverse events (AEs), and occurrence of antidrug antibodies. Thromboembolic events were AEs of special interest. Thirty-six patients with HA, 15 with HAwI, and 10 with HBwI were exposed to concizumab. Estimated ABRs during the main 1 extension parts at last dose level were 4.8 (95% confidence interval [CI], 3.2-7.2) and 6.4 (95% CI, 4.1-9.9) in explorer4 and explorer5, respectively (spontaneous ABRs were 1.8 [95% CI, 1.2-2.6] and 2.1 [95% CI, 1.3-3.3]). Most AEs were mild, with no deaths, events leading to withdrawal, or thromboembolic events. Anti-drug antibodies developed in 25% of patients and were low titer and transient, with no observed clinical effect in most cases. Results of the main 1 extension parts of these trials were consistent with results of the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypes
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-06-14
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/707460
https://dx.doi.org/10.1182/bloodadvances.2021006403
url http://hdl.handle.net/10486/707460
https://dx.doi.org/10.1182/bloodadvances.2021006403
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Hematology
publisher.none.fl_str_mv American Society of Hematology
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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