Roche's Investigational Anti-IL-33/ST2 Antibody for COPD Misses Phase 3 Primary Endpoint

Topline results from 2 pivotal studies of astegolimab in chronic obstructive pulmonary disease (COPD) demonstrated divergent outcomes on the primary endpoint, according to a July 21 announcement from developer Roche.¹

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In the phase 2b ALIENTO trial² (n = 1,301), astegolimab administered every 2 weeks met its primary endpoint, reducing the COPD annualized exacerbation rate (AER) at 52 weeks by a statistically significant 15.4% compared with placebo. However, the phase 3 ARNASA study³ (n = 1,375) did not meet the primary endpoint. Although a numerical reduction in AER of 14.5% was observed at 52 weeks, the difference was not statistically significant. Astegolimab was administered on top of standard of care maintenance therapy in both studies, the company said.¹

Both studies enrolled a broad population of former and current smokers with moderate to very severe COPD and a history of frequent exacerbations, regardless of blood eosinophil count. Roche noted that the overall number of exacerbations was lower than anticipated in both trials and that secondary endpoints were generally consistent across ALIENTO and ARNASA. The safety profile of astegolimab was in line with previous reports, with no new safety signals identified.^2,3

"While COPD remains the third leading cause of death worldwide, patients and families have limited treatment options for managing this debilitating and complex disease," Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, said in the statement. "This was the first set of studies in an ‘all-comers’ COPD population, and we will discuss these data with regulatory authorities to evaluate next steps for astegolimab.”¹

Astegolimab is a fully human investigational anti-ST2 monoclonal antibody that blocks IL-33 signaling by binding with high affinity to the ST2 receptor. Both ALIENTO (NCT05037929)¹ and ARNASA (NCT05595642) were double-blind, placebo-controlled, multicenter studies evaluating astegolimab given every 2 or 4 weeks in addition to standard COPD maintenance regimens, including inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA); long-acting muscarinic antagonist (LAMA) plus LABA; ICS plus LAMA plus LABA. The primary efficacy endpoint for both trials was the annualized rate of moderate and severe COPD exacerbations over 52 weeks.¹

Roche plans to present detailed data from both trials at an upcoming medical meeting and to discuss results with regulatory authorities.

References

1. Roche provides update on astegolimab in chronic obstructive pulmonary disease. News release. Roche. July 21, 2025. Accessed July 21, 2025. https://www.roche.com/media/releases/med-cor-2025-07-21

2. A study to evaluate astegolimab in participants with chronic obstructive pulmonary disease (ARNASA). ClinicalTrials.gov NCT05595642. Updated July 30, 2025. Accessed July 21, 2025. https://clinicaltrials.gov/study/NCT05595642

3. A study to evaluate the efficacy and safety of astegolimab in participants with chronic obstructive pulmonary disease. ClinicalTrials.gov NCT05037929.. Updated July 20, 2025. Accessed July 21, 2025. https://clinicaltrials.gov/study/NCT05037929