Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study
Abstract Background Berotralstat (BCX7353) is an oral, once‐daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongo...
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Wiley
2021-06-01
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Series: | Clinical and Translational Allergy |
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Online Access: | https://doi.org/10.1002/clt2.12035 |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Henriette Farkas Marcin Stobiecki Jonny Peter Tamar Kinaciyan Marcus Maurer Emel Aygören‐Pürsün Sorena Kiani‐Alikhan Adrian Wu Avner Reshef Anette Bygum Olivier Fain David Hagin Aarnoud Huissoon Miloš Jeseňák Karen Lindsay Vesna Grivcheva Panovska Urs C. Steiner Celia Zubrinich Jessica M. Best Melanie Cornpropst Daniel Dix Sylvia M. Dobo Heather A. Iocca Bhavisha Desai Sharon C. Murray Eniko Nagy William P. Sheridan |
spellingShingle |
Henriette Farkas Marcin Stobiecki Jonny Peter Tamar Kinaciyan Marcus Maurer Emel Aygören‐Pürsün Sorena Kiani‐Alikhan Adrian Wu Avner Reshef Anette Bygum Olivier Fain David Hagin Aarnoud Huissoon Miloš Jeseňák Karen Lindsay Vesna Grivcheva Panovska Urs C. Steiner Celia Zubrinich Jessica M. Best Melanie Cornpropst Daniel Dix Sylvia M. Dobo Heather A. Iocca Bhavisha Desai Sharon C. Murray Eniko Nagy William P. Sheridan Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study Clinical and Translational Allergy berotralstat hereditary angioedema long‐term prophylaxis safety |
author_facet |
Henriette Farkas Marcin Stobiecki Jonny Peter Tamar Kinaciyan Marcus Maurer Emel Aygören‐Pürsün Sorena Kiani‐Alikhan Adrian Wu Avner Reshef Anette Bygum Olivier Fain David Hagin Aarnoud Huissoon Miloš Jeseňák Karen Lindsay Vesna Grivcheva Panovska Urs C. Steiner Celia Zubrinich Jessica M. Best Melanie Cornpropst Daniel Dix Sylvia M. Dobo Heather A. Iocca Bhavisha Desai Sharon C. Murray Eniko Nagy William P. Sheridan |
author_sort |
Henriette Farkas |
title |
Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study |
title_short |
Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study |
title_full |
Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study |
title_fullStr |
Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study |
title_full_unstemmed |
Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S study |
title_sort |
long‐term safety and effectiveness of berotralstat for hereditary angioedema: the open‐label apex‐s study |
publisher |
Wiley |
series |
Clinical and Translational Allergy |
issn |
2045-7022 |
publishDate |
2021-06-01 |
description |
Abstract Background Berotralstat (BCX7353) is an oral, once‐daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long‐term safety study of berotralstat in patients with HAE. Methods APeX‐S is an ongoing, phase 2, open‐label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE‐C1‐INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long‐term safety and the secondary objective was to evaluate effectiveness. Results Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11–540) and 307 (14–429) days for the 150‐mg and 110‐mg groups, respectively. Treatment‐emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug‐related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug‐related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. Conclusions In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. Trial registration The study is registered with ClinicalTrials.gov (NCT03472040). |
topic |
berotralstat hereditary angioedema long‐term prophylaxis safety |
url |
https://doi.org/10.1002/clt2.12035 |
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doaj-857745995f5542e9849cc3caa86d3acb2021-09-14T11:50:27ZengWileyClinical and Translational Allergy2045-70222021-06-01114n/an/a10.1002/clt2.12035Long‐term safety and effectiveness of berotralstat for hereditary angioedema: The open‐label APeX‐S studyHenriette Farkas0Marcin Stobiecki1Jonny Peter2Tamar Kinaciyan3Marcus Maurer4Emel Aygören‐Pürsün5Sorena Kiani‐Alikhan6Adrian Wu7Avner Reshef8Anette Bygum9Olivier Fain10David Hagin11Aarnoud Huissoon12Miloš Jeseňák13Karen Lindsay14Vesna Grivcheva Panovska15Urs C. Steiner16Celia Zubrinich17Jessica M. Best18Melanie Cornpropst19Daniel Dix20Sylvia M. Dobo21Heather A. Iocca22Bhavisha Desai23Sharon C. Murray24Eniko Nagy25William P. Sheridan26Hungarian Angioedema Center of Reference and Excellence Department of Internal Medicine and Hematology Semmelweis University Budapest HungaryDepartment of Clinical and Environmental Allergology Jagiellonian University Medical College Krakow PolandAllergy and Immunology Unit University of Cape Town Lung Institute Cape Town South AfricaDepartment of Dermatology Medical University of Vienna Vienna AustriaDermatological Allergology Department of Dermatology and Allergy Charité ‐ Universitätsmedizin Berlin Berlin GermanyDepartment for Children and Adolescents University Hospital Frankfurt Goethe University Frankfurt Frankfurt GermanyDepartment of Immunology Barts Health NHS Trust Royal London Hospital London UKCenter for Allergy and Asthma Care Central Hong Kong ChinaAngioderma Center Barzilai University Medical Center Ashkelon IsraelDepartment of Dermatology and Allergy Centre Odense University Hospital Odense DenmarkSorbonne Université Service de Médecine Interne AP‐HP, Hôpital Saint‐Antoine Paris FranceAllergy and Clinical Immunology Unit Department of Medicine Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine University of Tel Aviv Tel Aviv IsraelDepartment of Immunology Birmingham Heartlands Hospital University Hospitals Birmingham UKNational Center for Hereditary Angioedema Department of Pediatrics Department of Pulmonology and Allergology Comenius University in Bratislava Jessenius Faculty of Medicine Martin SlovakiaAuckland DHB Clinical Immunology and Allergy Auckland New ZealandUniversity Clinic of Dermatology Ss Cyril and Methodius University Skopje MacedoniaDepartment of Immunology University Hospital Zurich Zurich SwitzerlandAllergy, Asthma and Clinical Immunology Alfred Health Melbourne Victoria AustraliaBioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USABioCryst Pharmaceuticals Durham North Carolina USAAbstract Background Berotralstat (BCX7353) is an oral, once‐daily inhibitor of plasma kallikrein recently approved for prevention of angioedema attacks in adults and adolescents with hereditary angioedema (HAE). The objective of this report is to summarize results from an interim analysis of an ongoing long‐term safety study of berotralstat in patients with HAE. Methods APeX‐S is an ongoing, phase 2, open‐label study conducted in 22 countries (ClinicalTrials.gov, NCT03472040). Eligible patients with a clinical diagnosis of HAE due to C1 inhibitor deficiency (HAE‐C1‐INH) were centrally allocated to receive berotralstat 150 or 110 mg once daily. The primary objective was to determine long‐term safety and the secondary objective was to evaluate effectiveness. Results Enrolled patients (N = 227) received berotralstat 150 mg (n = 127) or 110 mg (n = 100) once daily. The median (range) duration of exposure was 342 (11–540) and 307 (14–429) days for the 150‐mg and 110‐mg groups, respectively. Treatment‐emergent adverse events (TEAEs) occurred in 91% (n = 206) of patients. The most common TEAEs across treatment groups were upper respiratory tract infection (n = 91, 40%), abdominal pain (n = 57, 25%), headache (n = 40, 18%), and diarrhea (n = 31, 14%) and were mostly mild to moderate. Fifty percent (n = 113) of patients had at least one drug‐related adverse event (AE; 150 mg, n = 57 [45%]; 110 mg, n = 56 [56%]), and discontinuations due to AEs occurred in 19 (8%) patients (150 mg, n = 13 [10%]; 110 mg, n = 6 [6%]). Three (1.3%) patients experienced a drug‐related serious TEAE. Among patients who received berotralstat through 48 weeks (150 mg, n = 73; 110 mg, n = 30), median HAE attack rates were low in month 1 (150 mg, 1.0 attacks/month; 110 mg, 0.5 attacks/month) and remained low through 12 months (0 attacks/month in both dose groups). Mean HAE attack rates followed a similar trend, and no evidence for patient tolerance to berotralstat emerged. In both dose groups, angioedema quality of life scores showed clinically meaningful changes from baseline. Conclusions In this analysis, both berotralstat doses, 150 and 110 mg once daily, were generally well tolerated. Effectiveness results support the durability and robustness of berotralstat as prophylactic therapy in patients with HAE. Trial registration The study is registered with ClinicalTrials.gov (NCT03472040).https://doi.org/10.1002/clt2.12035berotralstathereditary angioedemalong‐termprophylaxissafety |