GARADACIMAB ELICITS ATTACK-FREE STATUS IN HEREDITARY ANGIOEDEMA INDEPENDENT OF BASELINE CHARACTERISTICS

Abstract

Introduction

Hereditary angioedema (HAE) attacks are recurrent, unpredictable, debilitating, and potentially life-threatening. Current guidelines state HAE treatment goals are complete disease control and normalization of life. Garadacimab, a fully human, once-monthly, anti-activated factor XII monoclonal antibody, was evaluated as HAE long-term prophylaxis in the pivotal Phase 3 (VANGUARD) study, and 62% of garadacimab-treated patients were attack-free (all patients receiving placebo experienced attacks). This post hoc analysis evaluated potential association between baseline patient characteristics and attack-free status.

Methods

In the 6-month, randomized, pivotal Phase 3 (VANGUARD) study, patients received garadacimab 200 mg subcutaneously (n=39) or placebo (n=25) once monthly. Patients treated with garadacimab who were attack-free (n=24) vs those with ≥1 attack (n=15) were compared across patient characteristics: age, body mass index, age at diagnosis, attacks per month during the run-in period, rate of mild/moderate/severe attacks during the run-in period, and combined rate of moderate/severe attacks during the run-in period. Youden-index was calculated for each characteristic, whereby 0 indicates no predictive ability for attack-free status and 1 indicates perfect predictive ability.

Results

All evaluated characteristics had low predictive ability for attack-free status (Youden-index range 0.18–0.39; sensitivity 25.0–79.2%; specificity 53.3–93.3%; Table). Attacks per month during the run-in period had the highest predictive power, but still had a low ability to predict attack-free status (Youden-index 0.39).

Conclusion

In the pivotal Phase 3 (VANGUARD) study, patients with HAE achieved attack-free status with garadacimab independently of evaluated baseline patient characteristics. Regardless of baseline characteristics, patients with HAE have the potential to achieve attack-free status with garadacimab.