Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)

Hereditary
angioedema (HAE) is a rare and potentially life-threatening
disease that affects an estimated 1 in 50 000 individuals worldwide.
Until recently, prophylactic HAE treatment options were limited to
injectables, a burdensome administration route that has driven the
need for an oral treatment. A substantial body of evidence has shown
that potent and selective plasma kallikrein inhibitors that block
the generation of bradykinin represent a promising approach for the
treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals
using a structure-guided drug design strategy) is a synthetic plasma
kallikrein inhibitor that is potent and highly selective over other
structurally related serine proteases. This once-daily, small-molecule
drug is the first orally bioavailable prophylactic treatment for HAE
attacks, having successfully completed a Phase III clinical trial
(meeting its primary end point) and recently receiving the U.S. Food
and Drug Administration’s approval for the prophylactic treatment
of HAE attacks in patients 12 years and older.