B15-03 Astegolimab Decreases Exacerbation Risk in Patients With COPD With Frequent Exacerbations, Irrespective of Blood Eosinophil Count: Pooled Analysis of the Pivotal Randomized Trials ALIENTO and ARNASA

Rationale The efficacy and safety of astegolimab (anti-ST2 monoclonal antibody) in patients with COPD with frequent exacerbations were evaluated in two randomized, double-blind, placebo-controlled trials: Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642). Here, we present results from prespecified pooled analyses of both studies. Methods Both trials randomized patients with COPD (ALIENTO: aged 40-90 years, ARNASA: aged 40-80 years) who were current/former smokers and had a history of frequent exacerbations, regardless of chronic bronchitis or blood eosinophil counts [BEC] 1:1:1 to receive 476 mg astegolimab subcutaneously Q2W or Q4W or placebo, added to optimized maintenance therapy, for a 52-week treatment period. The primary endpoint in both trials was the annualized rate of moderate and severe COPD exacerbations. Key secondary endpoints included proportion of participants with a decrease of ≥ 4 points SGRQ-C total score, annualized rate of severe COPD exacerbations, and safety. Results 2676 participants were included in the pooled modified intent-to-treat (ITT) population (astegolimab Q2W, n = 892; astegolimab Q4W, n = 896; placebo, n = 888). Pooled participant characteristics were generally balanced between arms. Compared with placebo, astegolimab Q2W significantly reduced the rate of moderate and severe COPD exacerbations by 14.7% (Figure; RR 0.853 [95% CI 0.759, 0.959]; P=0.0077); Q4W data are also included in the figure. This exacerbation rate reduction for astegolimab Q2W versus placebo was consistent across prespecified subgroups such as current/former smokers, baseline BEC, and chronic bronchitis. A greater reduction in exacerbation rate with astegolimab Q2W versus placebo was observed in those with a history of > 2 (vs 2) exacerbations, or moderate airflow obstruction (GOLD II) (vs very severe). Compared with placebo, astegolimab Q2W nominally reduced severe exacerbations (32% reduction; RR 0.68 [95% CI 0.52, 0.87]; P=0.0028) and increased the proportion of participants with ≥4-point decrease from baseline in SGRQ-C total score (odds ratio 1.35 [95% CI 1.11, 1.64]; P=0.0029). Astegolimab Q2W was well tolerated in the pooled population, with adverse event rates per 100 patient-years of 365, 403, and 408 for the Q2W, Q4W, and placebo arms, respectively. Conclusions In this pooled analysis of data from the ALIENTO and ARNASA trials, astegolimab Q2W versus placebo significantly reduced the rate of moderate and severe exacerbations by 14.7% over 52 weeks. There was also a clinically meaningful reduction in severe exacerbations and increase in proportion of participants with ≥4 improvement in SGRQ-C total score, consistent with results from individual trials. This abstract is funded by: This pooled analysis was sponsored by F. Hoffman-La Roche Ltd.