Therapeutics and Clinical Risk Management (Mar 2023)
Prevention of Recurrent Attacks of Hereditary Angioedema (HAE): Berotralstat and Its Oral Bioavailability
Abstract
Maximiliano Diaz-Menindez,1 Dan Morgenstern-Kaplan,2 Lyda Cuervo-Pardo,3 Santiago Alvarez-Arango,4,5 Alexei Gonzalez-Estrada6 1Division of Pulmonary, Allergy, and Sleep Medicine, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA; 2Department of Internal Medicine, University of Miami/Jackson Health System, Miami, FL, USA; 3Division of Rheumatology, Allergy and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL, USA; 4Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 6Division of Allergy, Asthma and Clinical Immunology, Department of Medicine, Mayo Clinic, Phoenix, AZ, USACorrespondence: Alexei Gonzalez-Estrada, Division of Pulmonary, Allergy and Sleep Medicine, Department of Medicine, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA, Tel +1 480-301-4284, Fax +1 480-301-4041, Email [email protected]: Hereditary angioedema (HAE) is a condition characterized by episodes of cutaneous and submucosal edema. Angioedema of the extremities and abdominal attacks are the most common manifestations of the disease. It can also affect the upper airways with the potential of becoming life-threatening. The two most common causes of HAE are a deficiency of C1 inhibitor (classified as type 1 HAE) or a dysfunction of C1 inhibitor (type 2 HAE). A malfunction or deficiency of C1 inhibitor leads to an overactivated plasma kallikrein (an inflammatory vasoactive peptide), that increases bradykinin, mediating the angioedema episodes in patients with HAE. To minimize the difficulties of this pathology and to improve patients’ quality of life, prevention of this condition is essential. Berotralstat is a unique option for oral administration for routine prophylaxis. This drug acts by binding to kallikrein and reducing its plasma activity, lowering bradykinin levels. Open-label studies have demonstrated the effectiveness of a single daily dose of berotralstat 150 mg in preventing HAE attacks. This review aims to examine studies performed to elucidate the efficacy, safety, and tolerability of berotralstat.Keywords: hereditary angioedema, berotralstat
