Garadacimab

The inflammation and swelling associated with attacks of hereditary angioedema (HAE) are primarily driven by bradykinin production. In types I and II HAE - which involve deficient or defective C1-INH - the contact system is overactivated, resulting in the continuous production of kallikrein and bradykinin. Type III HAE leads to increased activation of factor XII, the first factor in the contact system, which also results in an overproduction of bradykinin. Bradykinin increases vascular permeability, ultimately causing edema.

Garadacimab binds to the catalytic domain of activated factor XII and inhibits its catalytic activity. The inhibition of activated factor XII decreases the activation of prekallikrein to kallikrein and reduces the production of bradykinin, thereby inhibiting the cascade of events leading to an HAE attack.