Genentech (Roche)’s Astegolimab Shows Mixed Data for COPD

Genentech, a subsidiary of Roche, has reported mixed phase 3 data for its biologic astegolimab in people with moderate to very severe chronic obstructive pulmonary disease (COPD).

“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, chief medical officer and head of Global Product Development, said in a statement.1 “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.”

The company shared data from the pivotal Phase IIb ALIENTO (n = 1,301) and the Phase III ARNASA (n = 1,375) trials investigating astegolimab compared to placebo, on top of standard of care maintenance therapy, only one of which met its primary endpoint of reducing the annualized exacerbation rate (AER). Both studies included a broad population of people with COPD, with both former and current smokers, regardless of blood eosinophil count, who have a history of frequent exacerbations.

Astegolimab is an investigational, fully human anti-ST2 monoclonal antibody designed to bind with high affinity to the ST2 receptor and block IL-33 signaling. ALIENTO and ARNASA are both double-blinded, placebo-controlled, multi-center studies evaluating efficacy and safety of astegolimab administered every 2 or every 4 weeks. Standard of care maintenance therapy for both studies was one of the following combinations - inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA); long-acting muscarinic antagonist (LAMA) plus LABA; ICS plus LAMA plus LABA.

In the new data, the ALIENTO study met its primary endpoint, with astegolimab reducing the AER by a statistically significant 15.4% at 52 weeks, when given every 2 weeks. On the other hand, the ARNASA study did not meet the same primary endpoint, with a numerical 14.5% reduction at 52 weeks when astegolimab was given every 2 weeks. Secondary endpoint findings were similar in both studies. Genentech noted that the total number of exacerbations was lower than prospectively anticipated in both trials. Both trials demonstrated a consistent safety profile of astegolimab with previously reported data and no new safety signals. Detailed results from ALIENTO and ARNASA will be shared at an upcoming medical meeting.

The data represent another setback for astegolimab’s potential path to market, after Genentech previously axed its other investigational indications of asthma and COVID and pneumonia in 2021 after disappointing data readouts.2,3 Its future as a COPD treatment is uncertain, especially compared to the high rates of efficacy seen with the field's only currently FDA-approved biologic, dupilumab.

Approved under the name Dupixent, Sanofi and Regeneron's therapy has continued to demonstrate efficacy in the population. Recent pooled data from the phase 3 BOREAS and NOTUS trials presented at the American Thoracic Society (ATS) International Conference 2025 demonstrated that by week 12, compared with placebo, dupilumab improved pre-bronchodilator FEV1 (least squares [LS] mean difference, 83; 95% CI, 51-114] mL), post-bronchodilator FEV1 (LS mean difference, 72; 95% CI, 40-105 mL), post-bronchodilator FEV1/FVC (LS mean difference, 16; 95% CI, 9-23), and post-bronchodilator FEF25-75% (LS mean difference, 80; 95% CI, 44-116 mL/s). Investigators noted improvements were sustained up to week 52.4

In the ITT population, the LS mean difference vs placebo in pre-bronchodilator FEV1 at week 12 was 89 (95% CI, 52, 127) in former smokers (n = 661 dupilumab; n = 654 placebo) and 64 (95% CI, 20-109) mL in current smokers (n = 275 dupilumab; n = 282 placebo).4

REFERENCES

1. Genentech Provides Update on Astegolimab in Chronic Obstructive Pulmonary Disease. News release. July 21, 2025. https://www.businesswire.com/news/home/20250720149499/en/Genentech-Provides-Update-on-Astegolimab-in-Chronic-Obstructive-Pulmonary-Disease

2. Adams B. Roche chucks out phase 3 ipatasertib combo tests, midstage IL-33 asthma, BTKi arthritis trials in Q4 clear-out. Article. Fierce Biotech. February 4, 2021. https://www.fiercebiotech.com/biotech/roche-chucks-out-phase-3-ipatasertib-combo-tests-midstage-il-33-asthma-btki-arthritis

3. Adams B. Roche culls 2 COVID-19 drug hopefuls amid Q1 clear-out. Article. Fierce Biotech. April 21, 2021. https://www.fiercebiotech.com/biotech/roche-culls-two-covid-drug-hopefuls-amid-q1-clear-out

4. Han MK, Sciurba FC, Anzueto A, et al. Dupilumab Improves Lung Function in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Inflammation: A Pooled Analysis From the Phase 3 NOTUS and BOREAS Trials [abstract]. Am J Respir Crit Care Med 2025;211:A1369. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A1369