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Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial
Author(s) -
Ohsawa Isao,
Honda Daisuke,
Suzuki Yusuke,
Fukuda Tomoo,
Kohga Keisuke,
Morita Eishin,
Moriwaki Shinichi,
Ishikawa Osamu,
Sasaki Yoshihiro,
Tago Masaki,
Chittick Greg,
Cornpropst Melanie,
Murray Sharon C.,
Dobo Sylvia M.,
Nagy Eniko,
Van Dyke Sharon,
Reese Lacy,
Best Jessica M.,
Iocca Heather,
Collis Phil,
Sheridan William P.,
Hide Michihiro
Publication year - 2021
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14670
Subject(s) - medicine , hereditary angioedema , angioedema , placebo , randomization , randomized controlled trial , clinical endpoint , adverse effect , abdominal pain , attack rate , surgery , dermatology , epidemiology , alternative medicine , pathology
Abstract 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.