The potential of factor XII inhibitors in preventing hereditary angioedema attacks

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of subcutaneous and/or submucosal swelling (angioedema). Current HAE-specific medications primarily focus on either inhibiting plasma bradykinin or kallikrein, or replacing C1-esterase inhibitor, but they are frequently limited in efficacy and accessibility. In contrast, Factor XII (FXII) inhibitors may provide a novel therapeutic approach by targeting the contact system at an upstream level, potentially addressing some of these limitations.

This review explores the role of FXII in HAE and assesses FXII inhibition as a promising prophylactic treatment strategy. By synthesizing findings from both preclinical and clinical studies and real-world observational studies, the review highlights the efficacy, safety, and practical benefits of FXII inhibitors, such as garadacimab.

FXII inhibition represents a promising new strategy for HAE management and may address current unmet needs in prophylactic therapies. The early experiences of garadacimab highlights FXII as a viable and druggable target, paving the way for broader applications in bradykinin-mediated disorders. Despite its potential, uncertainties remain regarding long-term safety, cost, and accessibility. Future research will help redefine the role of FXII inhibition in advancing personalized care and improving the quality of life for patients with HAE.