Garadacimab for the long-term prophylaxis of hereditary angioedema.

Hereditary angioedema (HAE), a rare and debilitating disease characterized by recurrent and spontaneous attacks of tissue swelling, has a high unmet therapeutic need, with many patients experiencing insufficient disease control with current prophylactic treatments. The goal of HAE treatment as per guidelines is to achieve total disease control and to normalize patients' lives. Factor XII (FXII), the principal initiator of the contact system, ultimately regulates the kallikrein-kinin system. Activated FXII (FXIIa) converts plasma prekallikrein to plasma kallikrein, which cleaves high-molecular-weight kininogen to produce the vasoactive peptide bradykinin. In HAE pathophysiology, kallikrein-kinin system dysregulation results in excessive bradykinin production. The anti-FXIIa monoclonal antibody garadacimab is approved for long-term prophylaxis against HAE attacks. In the pivotal phase III (VANGUARD) and ongoing phase III open-label extension studies, garadacimab administered subcutaneously (2 × 200 mg loading dose followed by 200 mg once monthly) demonstrated durable efficacy with early onset of protection and a favorable long-term safety profile. Based on this and earlier clinical data, garadacimab has the potential to bring patients closer to achieving the guideline-recommended goals of disease control and normalization of life. Here, we provide an overview of the results from the garadacimab clinical development program.