Astegolimab for chronic obstructive pulmonary disease with frequent exacerbations: pooled analysis of the ALIENTO and ARNASA trials

Rationale: The efficacy and safety of astegolimab, an anti-ST2 monoclonal antibody, was evaluated in participants with chronic obstructive pulmonary disease (COPD) and frequent exacerbations in the pivotal ALIENTO and ARNASA trials. Objectives: To report the prespecified pooled analysis of ALIENTO and ARNASA. Methods: ALIENTO and ARNASA were randomized, double-blind, placebo-controlled trials with similar designs and included participants with COPD, a history of frequent exacerbations, and current/former smoking status, irrespective of blood eosinophil count and chronic bronchitis. Participants were randomized 1:1:1 to astegolimab 476 mg every 2 weeks (Q2W), astegolimab every 4 weeks (Q4W), or placebo for 52 weeks, plus optimized maintenance therapy. The primary endpoint was annualized rate of moderate/severe exacerbations. Secondary endpoints included annualized rate of severe exacerbations. A hierarchical statistical plan was followed with hypothesis testing of secondary efficacy endpoints gated on the primary efficacy endpoint success. Measurements and main results: A total of 2682 participants were included in the pooled intent-to-treat population. Astegolimab significantly reduced the annualized rate of moderate/severe exacerbations by 15% in the Q2W arm (adjusted rate ratio, 0.85 [95% CI, 0.76-0.96]; P = .0077) and by 12% in the Q4W arm (rate ratio, 0.88 [95% CI, 0.78-0.99]; P = .0265). -A -nominally significant reduction in the annualized rate of severe COPD exacerbations (rate ratio, 0.68 [95% CI, 0.52-0.87]; P = .0028) was observed for astegolimab Q2W vs placebo. Astegolimab was well tolerated. Conclusions: Astegolimab every 2 weeks reduced the annualized rate of moderate/severe exacerbations in a clinically heterogeneous population of participants with COPD and frequent exacerbations.