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.

Allergy and Asthma Clinical Research Walnut Creek Calif

Allergy and Asthma Specialists of Dallas Dallas Tex

Asthma and Allergy Specialists Charlotte NC

BioCryst Pharmaceuticals Durham NC

Clinical Research Center of Alabama Birmingham Ala

Clinique Spécialisée en Allergie de la Capitale Québec Canada

Department of Clinical Immunology and Allergology St Anne's University Hospital in Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Medicine and Pediatrics Penn State University Hershey Pa

Department of Pediatrics University of California Los Angeles Calif

Dermatological Allergology Department of Dermatology and Allergy Charité Universitätsmedizin Berlin Berlin Germany

Division of Clinical Immunology and Allergy Department of Medicine Icahn School of Medicine at Mount Sinai New York NY

Faculty Hospital Department of Allergology and Immunology Plzen Czech Republic

Hungarian Angioedema Reference Center 3rd Department of Internal Medicine Semmelweis University Budapest Hungary

Institute for Asthma and Allergy Chevy Chase Md

Little Rock Allergy and Asthma Clinical Research Center Little Rock Ark

Massachusetts General Hospital Harvard Medical School Boston Mass

Medical University of Vienna Department of Dermatology Vienna Austria

Optimed Research Ltd Columbus Ohio

Ottawa Allergy Research Corporation Department of Medicine University of Ottawa Ottawa Ontario Canada

Portland Clinical Research Portland Ore

University Hospital Frankfurt Goethe University Frankfurt Frankfurt Germany

University of California San Diego San Diego Calif

University of Cincinnati Cincinnati Ohio

University of Washington School of Medicine Marycliff Clinical Research Spokane Wash

Washington University School of Medicine St Louis Mo

J Allergy Clin Immunol. 2021 Jul;148(1):80-82. doi: 10.1016/j.jaci.2021.05.023. PubMed

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ClinicalTrials.gov
NCT03485911