Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

  • 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.

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Author:Bruce L. ZurawORCiDGND, William R. LumryORCiD, Douglas T. Johnston, Emel Aygören-PürsünORCiDGND, Aleena BanerjiGND, Jonathan A. BernsteinORCiDGND, Sandra C. Christiansen, Joshua S. JacobsORCiD, Karl V. Sitz, Richard G. GowerORCiD, Remi Gagnon, H. James WednerGND, Tamar KinaciyanORCiD, Roman HaklORCiD, Jana Hanzlíková, John T. Anderson, Donald L. McNeil, Stephen B. Fritz, William H. Yang, Raffi TachdjianORCiD, Paula J. BusseORCiD, Timothy J. Craig, H. Henry Li, Henriette FarkasORCiD, Jessica M. Best, Desiree Clemons, Melanie Cornpropst, Sylvia M. Dobo, Heather A. Iocca, Deborah Kargl, Eniko Nagy, Sharon C. Murray, Phil Collis, William P. SheridanORCiD, Marcus MaurerORCiDGND, Marc A. RiedlORCiDGND
Parent Title (English):The journal of allergy and clinical immunology
Place of publication:Amsterdam [u.a.]
Document Type:Article
Date of Publication (online):2020/10/21
Date of first Publication:2020/10/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/02/10
Tag:BCX7353; C1 inhibitor; HAE; berotralstat; efficacy; hereditary angioedema; kallikrein inhibitor; long-term prophylaxis; prophylaxis; safety
Page Number:18
First Page:164
Last Page:172.e9
This study was funded by BioCryst Pharmaceuticals, Inc. At Harvard Medical School, the study was conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health award UL1 TR001102).
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0