Matching-Adjusted Indirect Comparison Between Garadacimab and Donidalorsen for Long-Term Prophylaxis in Hereditary Angioedema
Author(s)
Imtiaz Samjoo, BSc, MSc, PhD1, Sarah Walsh, MSc1, Anja Haltner, MSc2, John Michael Sears, PhD, MBA3, Yinglei Li, PhD3, Simona Gavata-Steiger, MBA4, Mauricio Alvarez-Reyes, PhD, MSc5, Chrissy van Beurden-Tan, PhD6, Marco Campioni, PhD7.
1EVERSANA, Burlington, ON, Canada, 2EVERSANA, New York, NY, USA, 3CSL Behring, King of Prussia, PA, USA, 4CSL Behring AG, Bern, Switzerland, 5MARCP Ltd, Bristol, United Kingdom, 6CSL Behring, Küssnacht, Switzerland, 7CSL, Zurich, Switzerland.
1EVERSANA, Burlington, ON, Canada, 2EVERSANA, New York, NY, USA, 3CSL Behring, King of Prussia, PA, USA, 4CSL Behring AG, Bern, Switzerland, 5MARCP Ltd, Bristol, United Kingdom, 6CSL Behring, Küssnacht, Switzerland, 7CSL, Zurich, Switzerland.
OBJECTIVES: Garadacimab and donidalorsen have been evaluated in separate Phase 3 randomized controlled trials (RCTs) for the long-term prophylaxis (LTP) treatment of patients with hereditary angioedema (HAE). The European Medicines Agency granted market authorization to garadacimab in 2025 and orphan designation to donidalorsen in 2024. Given the absence of head-to-head studies, this analysis aims to estimate the relative efficacy between garadacimab subcutaneous (SC) 200 mg monthly and two doses of donidalorsen (80 mg SC every four weeks [Q4W]; every eight weeks [Q8W]) using matching-adjusted indirect comparisons.
METHODS: Individual patient data from the garadacimab Phase 3 RCT (VANGUARD [NCT04656418]) were reweighted to match published summary data from the donidalorsen phase 3 RCT (OASIS-HAE [NCT05139810]). Clinically important baseline characteristics including HAE attack rate during run-in, body mass index, age, and sex were adjusted for. Key efficacy outcomes from pivotal trials - time-normalized number of HAE attacks, time-normalized number of moderate and/or severe HAE attacks, and proportion of attack-free patients - were assessed. Sensitivity analyses were also conducted.
RESULTS: Compared with donidalorsen Q4W, garadacimab statistically significantly reduced the number of moderate and/or severe HAE attacks (rate ratio [RR]; 95% confidence interval: 0.18; 0.06, 0.60) and patients were twice as likely to be attack-free (hazard ratio [HR]: 2.21; 1.02, 4.79). The number of HAE attacks for patients receiving garadacimab was 39% lower than that of patients receiving donidalorsen Q4W, but this result was not statistically significant (RR: 0.61; 0.21, 1.75). Compared with donidalorsen Q8W, garadacimab was associated with statistically significant reductions in both the number of HAE attacks (RR: 0.21; 0.08, 0.54) and number of moderate and/or severe HAE attacks (RR: 0.09; 0.03, 0.26), and patients were three times as likely to be attack-free (HR: 3.02; 1.04, 8.79).
CONCLUSIONS: These findings demonstrate that garadacimab may provide improved therapeutic benefit compared to donidalorsen for LTP in HAE.
METHODS: Individual patient data from the garadacimab Phase 3 RCT (VANGUARD [NCT04656418]) were reweighted to match published summary data from the donidalorsen phase 3 RCT (OASIS-HAE [NCT05139810]). Clinically important baseline characteristics including HAE attack rate during run-in, body mass index, age, and sex were adjusted for. Key efficacy outcomes from pivotal trials - time-normalized number of HAE attacks, time-normalized number of moderate and/or severe HAE attacks, and proportion of attack-free patients - were assessed. Sensitivity analyses were also conducted.
RESULTS: Compared with donidalorsen Q4W, garadacimab statistically significantly reduced the number of moderate and/or severe HAE attacks (rate ratio [RR]; 95% confidence interval: 0.18; 0.06, 0.60) and patients were twice as likely to be attack-free (hazard ratio [HR]: 2.21; 1.02, 4.79). The number of HAE attacks for patients receiving garadacimab was 39% lower than that of patients receiving donidalorsen Q4W, but this result was not statistically significant (RR: 0.61; 0.21, 1.75). Compared with donidalorsen Q8W, garadacimab was associated with statistically significant reductions in both the number of HAE attacks (RR: 0.21; 0.08, 0.54) and number of moderate and/or severe HAE attacks (RR: 0.09; 0.03, 0.26), and patients were three times as likely to be attack-free (HR: 3.02; 1.04, 8.79).
CONCLUSIONS: These findings demonstrate that garadacimab may provide improved therapeutic benefit compared to donidalorsen for LTP in HAE.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO162
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Rare & Orphan Diseases