Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.
Japan
berotralstat
hereditary angioedema
kallikrein inhibitor
prophylaxis
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
23
10
2020
received:
02
07
2020
accepted:
08
11
2020
pubmed:
29
11
2020
medline:
29
6
2021
entrez:
28
11
2020
Statut:
ppublish
Résumé
With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period. Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%). Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.
Sections du résumé
BACKGROUND
With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients.
METHODS
APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period.
RESULTS
Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%).
CONCLUSIONS
Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.
Identifiants
pubmed: 33247955
doi: 10.1111/all.14670
pmc: PMC8247297
doi:
Substances chimiques
Complement C1 Inhibitor Protein
0
Pyrazoles
0
berotralstat
XZA0KB1BDQ
Banques de données
ClinicalTrials.gov
['NCT03873116']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1789-1799Informations de copyright
© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Références
Ann Allergy Asthma Immunol. 2015 Jun;114(6):492-8
pubmed: 25872948
Am J Med. 2006 Mar;119(3):267-74
pubmed: 16490473
Cardiovasc Hematol Agents Med Chem. 2009 Jul;7(3):234-50
pubmed: 19689262
Intern Med. 2018 Nov 1;57(21):3065-3066
pubmed: 30210137
Allergol Int. 2012 Dec;61(4):559-62
pubmed: 23093794
Allergy Asthma Proc. 2010 Sep-Oct;31(5):407-14
pubmed: 20929608
J Allergy Clin Immunol Pract. 2013 Sep-Oct;1(5):458-67
pubmed: 24565617
Int J Mol Sci. 2019 Aug 03;20(15):
pubmed: 31382625
Clin Rev Allergy Immunol. 2016 Oct;51(2):216-29
pubmed: 27459852
Acta Derm Venereol. 2015 Jul;95(6):706-10
pubmed: 25394853
Allergy. 2016 Aug;71(8):1203-9
pubmed: 27038109
Ann Allergy Asthma Immunol. 2013 Nov;111(5):329-36
pubmed: 24125136
Intern Med. 2018 Nov 1;57(21):3193-3197
pubmed: 29709957
Allergy. 2012 Oct;67(10):1289-98
pubmed: 22913638
Ann Allergy Asthma Immunol. 2010 Mar;104(3):193-204
pubmed: 20377108
J Allergy Clin Immunol. 2012 Sep;130(3):692-7
pubmed: 22841766
Drugs Context. 2019 Oct 02;8:212605
pubmed: 31645881
J Allergy Clin Immunol Pract. 2021 Jan;9(1):132-150.e3
pubmed: 32898710
N Engl J Med. 2018 Jul 26;379(4):352-362
pubmed: 30044938
Allergy Asthma Clin Immunol. 2019 Nov 25;15:72
pubmed: 31788005
Am J Manag Care. 2018 Aug;24(14 Suppl):S308-S313
pubmed: 30132645
J Allergy Clin Immunol. 2020 Oct 21;:
pubmed: 33098856