Long-term efficacy of garadacimab in patients with hereditary angioedema from the Phase 3 open-label extension study: an up to 3-year interim analysis
C. Katelaris1; A. Reshef2; H. Chapdelaine3; K. Yamagami4; ME. Manning5; I. Jacobs6; JP. Lawo7; Y. Li6; C. Nenci8; P. Staubach9
1Campbelltown Hospital, and Western Sydney University, Sydney, New South Wales, Australia; 2Allergy, Immunology and Angioedema Center, Barzilai University Hospital, Ashkelon, Israel; 3Montreal Clinical Research Institute, Montreal, Quebec, Canada; 4Osaka City General Hospital, Osaka, Japan; 5Allergy, Asthma & Immunology Associates, Ltd; UA College of Medicine – Phoenix, Phoenix, AZ, United States of America; 6CSL Behring, King of Prussia, PA, United States of America; 7CSL Innovation GmbH, Marburg, Germany; 8CSL Behring AG, Bern, Switzerland; 9University Medical Center Mainz, Johannes Gutenberg University of Mainz, Mainz, Germany
Background

Hereditary angioedema (HAE) is characterized by recurrent, unpredictable, and potentially life-threatening attacks. Garadacimab (anti-activated factor XII monoclonal antibody) has demonstrated early onset and durable protection against HAE attacks, with a favorable long-term safety profile across clinical studies. During the 6-month treatment period in the pivotal Phase 3 (VANGUARD) study, the mean monthly HAE attack rate was significantly lower in patients receiving garadacimab 200 mg subcutaneous (SC) once monthly (0.27) vs placebo (2.01; P<0.0001), corresponding to a difference of −87%. This latest analysis of the ongoing Phase 3 open-label extension (OLE; NCT04739059) includes long-term efficacy data for a maximum garadacimab exposure of 3.1 years.

Method

Exposure and HAE attack-rate data are reported for the Phase 3 OLE (data cutoff: June 15, 2024). HAE attack-free duration is reported using an integrated analysis of all patients who received garadacimab 200 mg SC once monthly across the clinical study program initiated in 2018.

Results

At data cutoff, 82.6% of patients (n=133/161) who entered the Phase 3 OLE and received ≥1 garadacimab dose were on treatment. Fifteen patients (9.3%) discontinued (adverse event: n=4; withdrawal by patient: n=3; site termination: n=3; physician decision: n=2; lack of efficacy, lost to follow-up, and pregnancy: n=1 each) and 13 (8.1%) completed the study. Median (interquartile range [IQR]) garadacimab exposure was 2.5 (2.2–2.7) years and 85.1% of patients (n=137/161) had ≥2 years of exposure (maximum exposure: 3.1 years). The mean (standard deviation [SD]) monthly HAE attack rate was 0.14 (0.34) during garadacimab treatment vs 3.57 (2.41) during run-in, corresponding to a 96.1% attack-rate reduction. Throughout the OLE, 50.3% of patients (n=81/161) were attack-free, with consistent proportions of attack-free patients in each 3-month exposure period (Figure). In an integrated analysis of the clinical study program based on 164 patients receiving garadacimab for 388 patient-years exposure, the median (IQR) maximum duration of HAE attack-free period was 2.2 (1.2–2.6) years.

Conclusion

Over a maximum exposure of 3.1 years in the Phase 3 OLE, garadacimab demonstrated durable efficacy in patients with HAE and led to sustained protection from attacks. Garadacimab has the potential to bring patients closer to achieving the HAE treatment goals of complete disease control and normalization of their lives.