Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.

Autor: Ohsawa I; Internal Medicine, Saiyu Soka Hospital, Saitama, Japan.; Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan., Honda D; Juntendo University Urayasu Hospital, Chiba, Japan., Suzuki Y; Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan., Fukuda T; Saitama Medical Center, Saitama, Japan., Kohga K; Community Hospital Kohga Hospital, Shizuoka, Japan., Morita E; Shimane University Hospital, Shimane, Japan., Moriwaki S; Osaka Medical College Hospital, Osaka, Japan., Ishikawa O; Gunma University Hospital, Gunma, Japan., Sasaki Y; National Hospital Organization Disaster Medical Center, Tokyo, Japan.; Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan., Tago M; Department of General Medicine, Saga University Hospital, Saga, Japan., Chittick G; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Cornpropst M; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Murray SC; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Dobo SM; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Nagy E; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Van Dyke S; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Reese L; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Best JM; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Iocca H; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Collis P; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Sheridan WP; BioCryst Pharmaceuticals, Inc, Durham, NC, USA., Hide M; Hiroshima University, Hiroshima, Japan.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2021 Jun; Vol. 76 (6), pp. 1789-1799. Date of Electronic Publication: 2020 Dec 23.
DOI: 10.1111/all.14670
Abstrakt: 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.
(© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: