LONG-TERM SAFETY AND EFFICACY WITH GARADACIMAB FOR HEREDITARY ANGIOEDEMA PROPHYLAXIS IN AN OPEN- LABEL EXTENSION STUDY

IntroductionHereditary angioedema (HAE) causes recurrent, debilitating attacks. Prophylaxis with garadacimab (anti-activated factor XII monoclonal antibody) demonstrated efficacy with a favorable safety profile in double-blind Phase 2 and pivotal Phase 3 (VANGUARD) studies. We report results from an ongoing open-label extension (OLE) study (NCT04739059).MethodsPatients received garadacimab 200 mg subcutaneously once-monthly. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with HAE-C1-INH. Secondary endpoints included monthly number of attacks and reduction in monthly number of attacks vs run-in.ResultsThe overall patient population (N=161) comprised Phase 2 roll-over (n=35), pivotal Phase 3 roll-over (n=57, including 21 previously receiving placebo), and newly enrolled patients (n=69). As of February 2023, median (interquartile range) garadacimab exposure was 13.8 months (11.9–16.3), and 119/161 patients (73.9%) had ≥12 months’ garadacimab exposure. Of 159 patients (safety analysis set), 133 (83.6%) experienced ≥1 TEAE. Most TEAEs (510/524, 97.3%) were mild/moderate. TEAEs experienced by ≥10% of patients were COVID-19 (57/159 patients, 35.8%), nasopharyngitis (27/159, 17.0%), and injection-site reactions (19/159, 11.9%). Three serious TEAEs (all unrelated to garadacimab) occurred. No TEAEs of special interest defined per protocol occurred (thromboembolic events, abnormal bleeding events, severe hypersensitivity including anaphylaxis). Mean (standard deviation) monthly number of attacks was 0.16 (0.37) during garadacimab vs 3.57 (2.41) during run-in, corresponding to a 94.7% (12.0) reduction. Consistent percentages of attack-free patients were observed over time across treatment windows (see Figure).ConclusionConsistent with Phase 2 and 3 studies, garadacimab demonstrated a favorable safety profile in the long term, accompanied by durable efficacy.