A review of oral kallikrein inhibitor berotralstat for hereditary angioedema.

Orladeyo, a once-daily oral formulation of berotralstat (formerly BCX-7353), is a novel oral small-molecule drug developed by BioCryst Pharmaceuticals for the prevention of hereditary angioedema (HAE) attacks. It was first approved by the U.S. Food and Drug Administration (FDA) in 2020, and in 2021 also gained approval for marketing in Japan and the European Union. Preclinical and phase I studies showed promising efficacy and safety, and several multicenter international Angioedema Prophylaxis (APeX) phase II and III trials have since been initiated to further evaluate berotralstat. The ongoing phase III APeX-2 trial showed a 67% reduction in HAE attacks at the standard 150-mg dosing. Mild to moderate gastrointestinal side effects are most commonly seen and minimal serious adverse effects have been reported. Other first-line therapies for HAE prophylaxis rely on burdensome subcutaneous or intravenous routes. Thus far berotralstat has shown to be effective and well tolerated for HAE prophylaxis with the convenience of once-daily oral dosing.