Berotralstat Plasma kallikrein (KLKB1) inhibitor Treatment of hereditary angioedema attacks

Hereditary angioedema (HAE) with C1 esterase inhibitor deficiency is a rare, but potentially life-threatening disease, characterized by recurrent self-limiting bouts of edema. Berotralstat (Biocryst Pharmaceuticals), a small molecule, is a potent and specific inhibitor of human plasma kallikrein activity. In a phase II study, a berotralstat oral liquid formulation showed efficacy for the acute treatment of HAE. In phase II and III studies, once-daily oral berotralstat showed efficacy and was well tolerated as a prophylactic agent for HAE attacks. Currently, the long-term safety of berotralstat is being assessed in a phase II/III study, and in an ongoing phase III study for the prevention of attacks in Japanese patients with HAE. Berotralstat has been granted Sakigake designation by the Japanese authorities; orphan drug designation by the U.S., the E.U. and Japan; fast track designation by the U.S.; and Promising Innovative Medicine designation by the U.K. for the prevention and/or treatment of angioedema attacks. In December 2020, the U.S. FDA approved berotralstat for prophylaxis to prevent attacks of HAE in adults and pediatric patients.