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

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.

• Authors: Isao Ohsawa, Daisuke Honda, Yusuke Suzuki, Tomoo Fukuda, Keisuke Kohga, Eishin Morita, Shinichi Moriwaki, Osamu Ishikawa, Yoshihiro Sasaki, Masaki Tago, Greg Chittick, Melanie Cornpropst, Sharon C Murray, Sylvia M Dobo, Eniko Nagy, Sharon Van Dyke, Lacy Reese, Jessica M Best, Heather Iocca, Phil Collis, William P Sheridan, Michihiro Hide
• Journal: Allergy (Allergy) Vol. 76 Issue 6 Pg. 1789-1799 (06 2021) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 33247955 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Chemical References

• Complement C1 Inhibitor Protein
• Pyrazoles
• berotralstat

Topics

• Angioedemas, Hereditary (diagnosis, drug therapy, epidemiology)
• Complement C1 Inhibitor Protein (adverse effects)
• Humans
• Japan (epidemiology)
• Prospective Studies
• Pyrazoles