Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial.
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.
['Ohsawa|Isao|I|', 'Honda|Daisuke|D|', 'Suzuki|Yusuke|Y|', 'Fukuda|Tomoo|T|', 'Kohga|Keisuke|K|', 'Morita|Eishin|E|', 'Moriwaki|Shinichi|S|', 'Ishikawa|Osamu|O|', 'Sasaki|Yoshihiro|Y|', 'Tago|Masaki|M|', 'Chittick|Greg|G|', 'Cornpropst|Melanie|M|', 'Murray|Sharon C|SC|', 'Dobo|Sylvia M|SM|', 'Nagy|Eniko|E|', 'Van Dyke|Sharon|S|', 'Reese|Lacy|L|', 'Best|Jessica M|JM|', 'Iocca|Heather|H|', 'Collis|Phil|P|', 'Sheridan|William P|WP|0000-0001-8320-1323', 'Hide|Michihiro|M|0000-0002-1569-6034']
D054179:Angioedemas, Hereditary D050718:Complement C1 Inhibitor Protein D006801:Humans D007564:Japan D011446:Prospective Studies D011720:Pyrazoles
berotralstat prophylaxis hereditary angioedema Japan kallikrein inhibitor