Abstract Rationale The efficacy and safety of astegolimab (anti-ST2 monoclonal antibody) in patients with COPD with frequent exacerbations was evaluated in two randomized, double-blind, placebo-controlled trials: Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642). The results from ALIENTO have been reported previously. Here, we present results from ARNASA. Methods Patients with COPD (aged 40-80 years, current/former smokers, and ≥2 moderate or severe exacerbations within previous 12 months, regardless of baseline blood eosinophil count and chronic bronchitis) were randomized (1:1:1) to receive 476 mg astegolimab subcutaneously Q2W or Q4W or placebo, added to optimized maintenance therapy, for 52 weeks. The primary endpoint was annualized rate of moderate and severe COPD exacerbations during the 52-week treatment period. Key secondary endpoints included time to first moderate/severe COPD exacerbation, SGRQ-C total score (mean change from baseline and proportion of participants achieving clinically meaningful improvement decrease of ≥ 4 points), annualized rate of severe COPD exacerbations, mean change from baseline in FEV1, and safety. Results 1375 participants were treated in the modified ITT population (astegolimab Q2W, n = 459; astegolimab Q4W, n = 459; placebo, n = 457). Participant characteristics were generally balanced between arms and 74.4% were receiving ICS/LABA/LAMA at baseline. A non-statistically significant 14.5% reduction in annualized rate of moderate or severe COPD exacerbations (primary endpoint) was observed for astegolimab Q2W versus placebo (Figure A; rate ratio RR 0.855 95% CI 0.722, 1.011; P=0.0675); see Figure A for Q4W versus placebo. This numerical exacerbation rate reduction for astegolimab Q2W versus placebo was consistent across prespecified subgroups, including current/former smokers and those with chronic bronchitis at baseline (Figure B). Astegolimab Q2W achieved a clinically meaningful reduction in severe exacerbations (33.1% reduction; RR 0.669 95% CI 0.472, 0.948; P=0.0238 and increase in the proportion of participants with ≥4-point decrease from baseline in SGRQ-C total score (odds ratio 1.49 95% CI 1.14, 1.96; P=0.0037). Directionally consistent results, numerically favoring astegolimab Q2W versus placebo, were also observed for time to first moderate/severe exacerbation, and mean change from baseline in SGRQ-C total score. No differences were seen in other secondary endpoints such as FEV1. Astegolimab was well tolerated, with comparable proportions of patients experiencing ≥1 AE across the 3 study arms (Q2W, 83.2%; Q4W, 87.9%; placebo, 85.5%). Conclusions Although the primary endpoint was not met in ARNASA, a clinically meaningful treatment effect of astegolimab Q2W versus placebo was observed for key efficacy endpoints. These results were consistent with those reported previously for ALIENTO. This abstract is funded by: This study was sponsored by F. Hoffman-La Roche Ltd.
Papi et al. (Fri,) studied this question.