Garadacimab in Hereditary Angioedema: Modeling Suggests Sustained Improvements in Attack-Free Probability and Quality of Life Over 5 Years.

Hereditary angioedema (HAE) attacks are recurrent, debilitating, and potentially life-threatening. Across the clinical program, garadacimab long-term prophylaxis demonstrated early onset and durable, sustained protection against HAE attacks and clinically meaningful improvements in health-related quality of life (HRQoL). HAE treatment goals include total disease control (attack-free) and normalization of life. Predicting treatment effect may aid shared decision-making and choice of long-term prophylaxis. Here, we report an attack-free probability model predicting garadacimab treatment effect beyond available Phase 3 clinical data and explore the relationship between HRQoL and attack-free duration. A generalized mixed-effect Poisson model was developed and validated with data from the garadacimab pivotal Phase 3 (VANGUARD) and Phase 3 open-label extension studies. Efficacy variables, including attack-free probabilities, were predicted for simulated populations of garadacimab-treated patients and assessed for goodness of fit. Analysis of covariance was used to assess the relationship between Angioedema Quality of Life questionnaire scores and attack-free duration. Model-predicted efficacy variables adequately reflected observed clinical data with high goodness of fit (Nakagawa-Schielzeth conditional R