Long-term quality-of-life and patient-reported improvements with garadacimab for hereditary angioedema: phase 3 open-label extension study

IntroductionHereditary angioedema (HAE) attacks impair quality of life (QoL). Garadacimab (anti-activated factor XII monoclonal antibody) reduced attacks in pivotal Phase 3 (VANGUARD; mean, 87%; median, 100% vs placebo) and ongoing open-label extension (OLE) studies (NCT04739059; mean, 95%; median, 100% vs run-in). OLE QoL and patient-reported outcomes (PROs) are reported.MethodsPatients received garadacimab 200 mg subcutaneous once-monthly. Previous garadacimab exposure cohort (n=71) received garadacimab in completed Phase 2 or 3 studies. Garadacimab-naïve cohort (n=90) comprised Phase 3 placebo (n=21/90) and newly enrolled patients (n=69/90). Angioedema-QoL (AE-QoL; exploratory endpoint) and Subject's Global Assessment of Response to Therapy (SGART [PRO]; secondary endpoint) were evaluated.ResultsMedian (interquartile range) garadacimab 200 mg exposures were 21.9 (17.7–37.4) and 13.3 (12.2–14.4) months for previous garadacimab exposure and garadacimab-naive cohorts, respectively.Mean total AE-QoL score improvements observed in the pivotal Phase 3 study were sustained in the previous garadacimab exposure cohort (Figure). At OLE Month 12, 81.6% of evaluable patients (n=40/49) had either stable or further clinically important (≥6 point decrease from final AE QoL score in previous study) QoL improvements.Mean total AE-QoL score improvements in the garadacimab-naïve cohort were similar to the pivotal phase 3 study (Figure). At OLE Month 12, 92.1% of evaluable patients (n=58/63) achieved clinically important (≥6 point decrease from Day 1) QoL improvements.For SGART, similar proportions of patients rated their garadacimab response as ‘good’ or better in pivotal Phase 3 (81.6%; n=31/38) and OLE (93.2%; n=110/118) studies.ConclusionGaradacimab elicited clinically meaningful and long-term QoL and PRO improvements.