Allergy Asthma Proc. 2025 May 1;46(3):200-208. doi: 10.2500/aap.2025.46.250026.
ABSTRACT
Background: Hereditary angioedema (HAE) is associated with substantial health-related quality of life (HRQoL) impairments. Complete disease control and life normalization are key treatment goals. In previous studies, garadacimab prevented HAE attacks with a favorable safety profile and HRQoL improvements. Objective: HRQoL was evaluated in patients with HAE receiving garadacimab stratified by attack-free status. Methods: In the pivotal phase III study (NCT04656418), 39 patients received garadacimab 200 mg subcutaneously once monthly and 25 volume-matched placebo. In the phase III open-label extension (OLE), 90 patients in the garadacimab-naive group (received placebo in previous studies or newly enrolled) and 71 patients in the previous garadacimab exposure group (received garadacimab in previous studies) received garadacimab (NCT04739059). Patients ages ≥ 18 years completed the Angioedema Quality of Life (AE-QoL) questionnaire in both studies; scores were evaluated post hoc by attack-free status. Results: In the pivotal phase III and phase III OLE studies, 62% and 60% of patients, respectively, were attack-free. In the pivotal phase III study, the mean AE-QoL total score improved with garadacimab, from 38.8 (day 1) to 6.6 (month 6) for attack-free patients (n = 19) and to 18.4 for patients with one or more attacks (n = 14) versus a change in mean AE-QoL total score from 43.7 to 40.5 with placebo (n = 20). In the phase III OLE study, the mean AE-QoL total score for patients who were garadacimab naive decreased from 46.2 (day 1) to 8.6 (month 12) for attack-free patients (n = 34) and from 54.5 to 23.5 for patients with one or more attacks (n = 30). For the previous garadacimab exposure group, AE-QoL improvements were maintained from previous studies, regardless of attack-free status. Conclusion: Garadacimab was associated with HRQoL improvement versus run-in in all groups. After garadacimab exposure in previous studies, improvements were maintained in the phase III OLE study. Attack-free patients had the greatest HRQoL improvements, bringing them closer to complete disease control and life normalization.Clinical trials NCT04656418, NCT04739059, <ext-link xmlns:xlink=»http://www.w3.org/1999/xlink» ext-link-type=»uri» xlink:href=»http://www.clinicaltrials.gov»>www.clinicaltrials.gov</ext-link>.
PMID:40380356 | DOI:10.2500/aap.2025.46.250026
