Isao Ohsawa1,2, Daisuke Honda3, Yusuke Suzuki2, Tomoo Fukuda4, Keisuke Kohga5, Eishin Morita6, Shinichi Moriwaki7, Osamu Ishikawa8, Yoshihiro Sasaki9,10, Masaki Tago11, Greg Chittick12, Melanie Cornpropst12, Sharon C Murray12, Sylvia M Dobo12, Eniko Nagy12, Sharon Van Dyke12, Lacy Reese12, Jessica M Best12, Heather Iocca12, Phil Collis12, William P Sheridan12, Michihiro Hide13. 1. Internal Medicine, Saiyu Soka Hospital, Saitama, Japan. 2. Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. 3. Juntendo University Urayasu Hospital, Chiba, Japan. 4. Saitama Medical Center, Saitama, Japan. 5. Community Hospital Kohga Hospital, Shizuoka, Japan. 6. Shimane University Hospital, Shimane, Japan. 7. Osaka Medical College Hospital, Osaka, Japan. 8. Gunma University Hospital, Gunma, Japan. 9. National Hospital Organization Disaster Medical Center, Tokyo, Japan. 10. Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan. 11. Department of General Medicine, Saga University Hospital, Saga, Japan. 12. BioCryst Pharmaceuticals, Inc, Durham, NC, USA. 13. Hiroshima University, Hiroshima, Japan.
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.
RCT Entities:
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: Marcus Maurer; Markus Magerl; Stephen Betschel; Werner Aberer; Ignacio J Ansotegui; Emel Aygören-Pürsün; Aleena Banerji; Noémi-Anna Bara; Isabelle Boccon-Gibod; Konrad Bork; Laurence Bouillet; Henrik Balle Boysen; Nicholas Brodszki; Paula J Busse; Anette Bygum; Teresa Caballero; Mauro Cancian; Anthony J Castaldo; Danny M Cohn; Dorottya Csuka; Henriette Farkas; Mark Gompels; Richard Gower; Anete S Grumach; Guillermo Guidos-Fogelbach; Michihiro Hide; Hye-Ryun Kang; Allen P Kaplan; Constance H Katelaris; Sorena Kiani-Alikhan; Wei-Te Lei; Richard F Lockey; Hilary Longhurst; William Lumry; Andrew MacGinnitie; Alejandro Malbran; Inmaculada Martinez Saguer; Juan José Matta Campos; Alexander Nast; Dinh Nguyen; Sandra A Nieto-Martinez; Ruby Pawankar; Jonathan Peter; Grzegorz Porebski; Nieves Prior; Avner Reshef; Marc Riedl; Bruce Ritchie; Farrukh Rafique Sheikh; William B Smith; Peter J Spaeth; Marcin Stobiecki; Elias Toubi; Lilian Agnes Varga; Karsten Weller; Andrea Zanichelli; Yuxiang Zhi; Bruce Zuraw; Timothy Craig Journal: World Allergy Organ J Date: 2022-04-07 Impact factor: 5.516