Bruce Zuraw1, William R Lumry2, Douglas T Johnston3, Emel Aygören-Pürsün4, Aleena Banerji5, Jonathan A Bernstein6, Sandra C Christiansen1, Joshua S Jacobs7, Karl V Sitz8, Richard G Gower9, Remi Gagnon10, H James Wedner11, Tamar Kinaciyan12, Roman Hakl13, Jana Hanzlíková14, John T Anderson15, Donald L McNeil16, Stephen B Fritz17, William H Yang18, Raffi Tachdjian19, Paula J Busse20, Timothy J Craig21, H Henry Li22, Henriette Farkas23, Jessica M Best24, Desiree Clemons24, Melanie Cornpropst24, Sylvia M Dobo24, Heather A Iocca24, Deborah Kargl24, Eniko Nagy24, Sharon C Murray24, Phil Collis24, William P Sheridan25, Marcus Maurer26, Marc A Riedl1. 1. University of California San Diego, San Diego, Calif. 2. Allergy & Asthma Specialists of Dallas, Dallas, Tex. 3. Asthma and Allergy Specialists, Charlotte, NC. 4. University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany. 5. Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 6. University of Cincinnati, Cincinnati, Ohio. 7. Allergy and Asthma Clinical Research, Walnut Creek, Calif. 8. Little Rock Allergy and Asthma Clinical Research Center, Little Rock, Ark. 9. University of Washington School of Medicine, Marycliff Clinical Research, Spokane, Wash. 10. Clinique Spécialisée en Allergie de la Capitale, Québec, Canada. 11. Washington University School of Medicine, St Louis, Mo. 12. Medical University of Vienna, Department of Dermatology, Vienna, Austria. 13. Department of Clinical Immunology and Allergology, St. Anne's University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic. 14. Faculty Hospital, Department of Allergology and Immunology, Plzen, Czech Republic. 15. Clinical Research Center of Alabama, Birmingham, Ala. 16. Optimed Research Ltd, Columbus, Ohio. 17. Portland Clinical Research, Portland, Ore. 18. Ottawa Allergy Research Corporation, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. 19. Department of Pediatrics, University of California, Los Angeles, Calif. 20. Division of Clinical Immunology and Allergy, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 21. Department of Medicine and Pediatrics, Penn State University, Hershey, Pa. 22. Institute for Asthma and Allergy, Chevy Chase, Md. 23. Hungarian Angioedema Reference Center, Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. 24. BioCryst Pharmaceuticals, Durham, NC. 25. BioCryst Pharmaceuticals, Durham, NC. Electronic address: bsheridan@biocryst.com. 26. Dermatological Allergology, Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND:Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS:APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS:A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
RCT Entities:
BACKGROUND:Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS:APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
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
Authors: Konrad Bork; John T Anderson; Teresa Caballero; Timothy Craig; Douglas T Johnston; H Henry Li; Hilary J Longhurst; Cristine Radojicic; Marc A Riedl Journal: Allergy Asthma Clin Immunol Date: 2021-04-19 Impact factor: 3.406
Authors: D A B Rex; K Deepak; Neelanchal Vaid; Shobha Dagamajalu; Richard Kumaran Kandasamy; Trude Helen Flo; T S Keshava Prasad Journal: J Cell Commun Signal Date: 2021-10-29 Impact factor: 5.782