Patient-Reported Outcomes in the Phase III OASIS-HAE Study of Donidalorsen for Hereditary Angioedema.

Abstract

Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, frequently severe swelling that negatively impacts patients' quality of life (QoL). In the phase III OASIS-HAE study (NCT05139810), donidalorsen reduced HAE attack rate, increased disease control, and improved QoL. Here, we report further analysis of donidalorsen's impact on QoL and other patient-reported outcomes (PROs). This double-blind, placebo-controlled study randomized patients with HAE to donidalorsen 80 mg or placebo once every 4 (Q4W) or 8 weeks (Q8W) over 24 weeks. PROs included Angioedema (AE)-QoL Questionnaire, Angioedema Control Test (AECT), Patient Global Impression of Severity (PGIS), and Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions (WPAI+CIQ). Ninety patients received donidalorsen Q4W (n = 45), donidalorsen Q8W (n = 23), or placebo (n = 22). A larger percentage of the donidalorsen Q4W group (88%) achieved clinically meaningful improvement (≥ 6-point reduction) in AE-QoL total score vs. placebo (45%). Both donidalorsen groups reported larger least-squares mean (LSM) changes from baseline to week 24 vs. placebo in AE-QoL functioning (difference: Q4W, -24.5; Q8W, -16.1), fears/shame (Q4W, -23.9; Q8W, -20.1), and nutrition (Q4W, -15.7; Q8W, -10.7) domains. Donidalorsen improved AECT scores vs. placebo (difference: Q4W, 6.0; Q8W, 4.1). A greater proportion of the donidalorsen Q4W group reported decreased disease severity vs. the placebo group (PGIS; 82% vs. 44%). Donidalorsen Q4W showed benefits vs. placebo in the presenteeism, overall work/school impairment, and activity impairment domains of the WPAI+CIQ. Donidalorsen significantly improved QoL and other PROs vs. placebo in patients with HAE.