Key takeaways
- The ALIENTO Phase IIb study met its primary endpoint, demonstrating a 15.4% reduction in annualized exacerbation rate with astegolimab administered every two weeks.
- The larger ARNASA Phase III study showed a 14.5% reduction in exacerbation rate but did not meet statistical significance, highlighting the importance of powering and endpoint planning in late-phase trials.
- Across all studies, astegolimab maintained a consistent safety profile, emphasizing its potential viability for further development despite mixed efficacy outcomes.
Roche has provided an update on its clinical development program evaluating astegolimab compared to placebo, plus standard of care maintenance therapy in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).1
Development program overview
The program is comprised of the Phase IIb ALIENTO study (NCT05037929) and the Phase III ARNASA trial (NCT05595642). Both share the same primary endpoint of statistically significant reduction in the annualized exacerbation rate (AER) at 52 weeks. ALIENTO met this primary endpoint with astegolimab administered every two weeks. However, ARNASA fell short of meeting the measurement.
"While COPD remains the third leading cause of death worldwide, patients and families have limited treatment options for managing this debilitating and complex disease," said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, in a press release. "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.”
Study outcomes
In ALIENTO, astegolimab reduced AER by 15.4% at 52 weeks, when given every two weeks, meeting the primary endpoint. Meanwhile, data from ARNASA demonstrated a 14.5% reduction at 52 weeks, when astegolimab was given every two weeks, missing the primary endpoint.
Roche added that results were generally consistent across secondary measures in both studies, exacerbations were lower than prospectively anticipated, and astegolimab’s safety profile was consistent with previously reported clinical data, with no new safety signals identified.
Study design and patient populations
The ALIENTO (Phase IIb) and ARNASA (Phase III) trials are both placebo-controlled, double-blind, multicenter studies evaluating the safety and effectiveness of astegolimab given every two or four weeks.
- Both trials enrolled current and former smokers with frequent COPD exacerbations, regardless of blood eosinophil levels, who were already receiving standard maintenance therapy.
- Maintenance therapies included combinations of inhaled corticosteroid (ICS) + long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA, or ICS + LAMA + LABA.
- ALIENTO included 1,301 patients and ARNASA included 1,375 patients in their initial analysis phases.
Earlier phase data from COPD-ST2OP
In May 2022, results from the Phase IIa COPD-ST2OP trial (NCT03615040) of astegolimab were published in The Lancet. According to the study authors, astegolimab did not significantly reduce exacerbation rate in patients with moderate to very severe COPD, but did improve health status when compared with placebo.2
Detailed results from the trial showed:
- The primary endpoint was not met, with no statistically significant reduction in exacerbation rates at 48 weeks between astegolimab and placebo groups (rate ratio 0.78; p=0.19).
- Patients in the eosinophil subgroup had slightly fewer exacerbations (0.69 vs. 0.83 for >170 eosinophils/μL).
- Patients receiving astegolimab reported a modest but statistically significant improvement in health-related quality of life (Saint George's Respiratory Questionnaire for COPD (SGRQ-C) score difference: –3.3; p=0.039).
- A non-significant trend toward better forced expiratory volume in one second (FEV1) was observed in the astegolimab group (+40 mL; p=0.094).
- Astegolimab significantly lowered both blood and sputum eosinophil counts compared to placebo (p<0.001 for both).
- Adverse event rates were similar across both treatment and placebo groups, indicating a generally well-tolerated safety profile.
Study design for COPD-ST2OP
The COPD-ST2OP trial was a single-center, randomized, double-blinded, placebo-controlled Phase IIa study to evaluate astegolimab in moderate to very severe COPD.
- Participants were randomly assigned 1:1 to receive either 490 mg subcutaneous astegolimab or placebo every four weeks for a total of 44 weeks.
- The primary outcome measured was the rate of COPD exacerbations over 48 weeks, evaluated using a negative binomial model with prespecified subgroup analyses based on baseline blood eosinophil counts.
- Secondary measures included changes in quality of life using the SGRQ-C score, lung function as measured by FEV₁, and both blood and sputum eosinophil counts.
- Safety was monitored through week 60 in all participants enrolled in the study.
References
1. [Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on astegolimab in chronic obstructive pulmonary disease. News release. Roche. July 20, 2025. Accessed July 23, 2025. https://www.roche.com/media/releases/med-cor-2025-07-21
2. Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial. Yousuf, Ahmed J et al. The Lancet Respiratory Medicine, Volume 10, Issue 5, 469 – 477. Accessed July 23, 2025. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00556-7/abstract
