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.

Clinical trial registration
ClinicalTrials.gov: NCT05037929; NCT05595642