CHARACTERIZATION OF INJECTION SITE-RELATED ADVERSE EVENTS WITH GARADACIMAB IN PATIENTS WITH HEREDITARY ANGIOEDEMA

Abstract

Introduction

Hereditary angioedema (HAE) is characterized by unpredictable, recurrent, and potentially life-threatening attacks. Garadacimab, a subcutaneous, once-monthly, fully human anti-activated factor XII monoclonal antibody in development for long-term prophylaxis (LTP), has demonstrated early and durable efficacy and favorable safety profile, and allowed most patients to achieve the HAE treatment goal of total disease control in clinical studies. Approved LTPs have demonstrated treatment-related injection-site reactions (e.g., pain, erythema, bruising). Patients have indicated a preference for new LTPs that reduce treatment burden. We characterize injection-site adverse events from the garadacimab Phase 3 clinical program.

Methods

Treatment-related injection-site reaction (ISR) data were analyzed from the pivotal Phase 3 (VANGUARD) and Phase 3 open-label extension (OLE) studies. Patient proportions, event numbers (E), and annualized rate (RY) data for ISRs were reported by study treatment group and preferred term within those groups.

Results

In the pivotal Phase 3 (VANGUARD) study (median garadacimab exposure: 5.98 months), 2/39 of garadacimab-treated patients (5.1%; E=3, RY=0.154) and 2/25 placebo-receiving patients (8.0%; E=2, RY=0.177) reported ISRs. Garadacimab-related ISRs were erythema, bruising, and pruritus (2.6% each; E=1, RY=0.051). Both placebo-related ISRs were erythema. In the Phase 3 OLE study (median garadacimab exposure: 13.8 months), 14/159 garadacimab-treated patients (8.8%; E=36, RY=0.195) reported ISRs – erythema (6.8%; E=14, RY=0.075), pruritus (2.5%; E=12, RY=0.065) and irritation (0.6%; E=1, RY=0.005; moderate, discontinuation at Month 6 upon patient decision).

Conclusion

In garadacimab Phase 3 studies, incidence of ISRs such as erythema, bruising and pruritus was low. The favorable injection-site tolerability with garadacimab may help reduce treatment burden during HAE LTP treatment.