Roche Weighs Next Steps for Astegolimab After Mixed COPD Trial Results
Contrasting outcomes for Roche’s investigational anti-ST2 monoclonal antibody treatment for COPD, mean the company needs to discuss the outcomes with regulatory authorities and evaluate next steps.
Roche has reported mixed topline results for two large studies of astegolimab, its experimental anti-ST2 monoclonal antibody intended to reduce exacerbations (sudden flare-ups of breathlessness and inflammation) in chronic obstructive pulmonary disease (COPD) (1). The two investigatory trials compared astegolimab to a placebo, on top of standard of care maintenance therapy for a broad population of patients — regardless of blood eosinophil count — with COPD that included both former and current smokers who have a history of frequent exacerbations.
The Phase IIb ALIENTO study met its primary endpoint by delivering a statistically significant (15.4%) relative reduction in annualized moderate-to-severe exacerbations compared with placebo over 52 weeks, and although the larger Phase III ARNASA trial also showed a decline in exacerbations (14.5%), it did not reach statistical significance.
With the total number of exacerbations lower than prospectively anticipated in both trials, Roche highlighted that the results were generally consistent across secondary endpoints in both studies, with the safety profile of astegolimab in line with previously reported data and with no new safety signals identified.
Despite the setback, Roche plans to present detailed results from both studies at an upcoming medical meeting and is currently in discussions with regulatory authorities to determine how to progress with the drug.
"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,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, in a company press release (1).
The results mirror those obtained from Sanofi and Regeneron’s joint venture evaluating itepekimab; the Phase III AERIFY-1 study met its primary endpoint by significantly reducing COPD exacerbations in former smokers, while the sister trial AERIFY-2 failed to achieve statistical significance despite showing positive results in a previous trial (2).
COPD is the fourth leading cause of death worldwide; causing 3.5 million deaths in 2021 (approximately 5% of all global deaths), and the eighth leading cause of poor health worldwide (3).
Despite its potential impact, biologic therapy is still in its infancy for treatment of COPD. In September 2024, the FDA granted approval for dupilumab (Sanofi and Regeneron) for patients with high blood eosinophil counts (4), with AstraZeneca’s anti-IL-5 antibody benralizumab still under regulatory review. A network meta-analysis of five drugs targeting type-2 inflammation estimates that dupilumab and benralizumab are the only candidates that can deliver clinically meaningful benefits — and largely in that same eosinophilic subgroup (5).
Against this backdrop, the large population of COPD sufferers will have to wait for a treatment that works independently of eosinophil status, offering significant market share to whichever company can successfully deliver such a treatment and making astegolimab one of the most closely watched programmes in the field.
References
Roche. [Ad Hoc Announcement Pursuant to Art. 53 LR] Roche Provides Update on Astegolimab in Chronic Obstructive Pulmonary Disease. Press Release, July 21, 2025.
Sanofi. Press Release: Itepekimab Met the Primary Endpoint in One of Two COPD Phase 3 Studies. Press Release, May 30, 2025.
WHO. Chronic Obstructive Pulmonary Disease (COPD). Fact Sheet, Nov. 6, 2024.
Sanofi. Press Release: Dupixent Approved in the US as the First-Ever Biologic Medicine for Patients with COPD. Press Release, Sept. 27, 2024.
Li, S.; Yi, B.; Wang, H.; et al. Efficacy and Safety of Biologics Targeting Type 2 Inflammation in COPD: A Systematic Review and Network Meta-Analysis. Int. J. Chron. Obstruct. Pulmon. Dis. 2025, (20), 2143–2159.