Efficacy and Safety of Subcutaneous Garadacimab for the Prophylaxis of Hereditary Angioedema Attacks in Adults and Adolescent Patients with HAE: Results from a Multicenter, Placebo-Controlled Phase 3 Trial

The efficacy and safety of garadacimab, a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII for the prevention of hereditary angioedema (HAE) attacks, were evaluated in a randomized, placebo-controlled, 6-month, Phase 3 trial (NCT04656418). Patients aged ≥12 years with type I/II HAE were randomized (3:2) to receive monthly subcutaneous (SC) garadacimab 200 mg or placebo after an initial SC loading dose of garadacimab 400 mg or volume-matched placebo. Efficacy, safety, and quality-of-life (QOL) measures were assessed. Once-monthly SC garadacimab significantly reduced the attack rate (AR) compared with placebo (p<0.001), resulting in an AR reduction of 86.5% (95% CI: 57.8–95.7). Adjusted for baseline AR, garadacimab-treated patients (n=39) experienced mean monthly ARs of 0.22 vs 2.07 for placebo-administered patients (n=24), resulting in an AR reduction vs placebo of 89.2% (95% CI: 75.6–95.2). Twenty-four (61.5%) garadacimab-treated patients were attack-free during the 6-month study, and 74.4% achieved ≥90% attack reduction vs the run-in period. The time to first attack was ≥72 days for 75% of garadacimab-treated patients vs 5 days for placebo-administered patients. Forty (62.5%) patients experienced ≥1 treatment-emergent adverse event (TEAE), totaling 129 events, including one severe, serious non-related TEAE (overnight hospital observation for laryngeal attack). The most common TEAEs were 5 mild injection-site reactions from 4 (6%) patients. No adverse events led to discontinuation. Angioedema-QOL total mean score improved by 23.7 points following first garadacimab administration. Once-monthly SC garadacimab was well tolerated throughout the treatment period and significantly reduced the AR vs placebo in patients with HAE.