Roche's Astegolimab for COPD: Mixed Trial Results in Intensifying Biologics Race
Chronic Obstructive Pulmonary Disease (COPD) is a serious and widespread lung condition that ranks as the third leading cause of death worldwide. It significantly impacts patients' quality of life, often leading to shortness of breath, coughing, and frequent flare-ups, known as exacerbations. Despite its prevalence, patients and their families currently face limited treatment options for managing this debilitating and complex disease. This challenging landscape has fueled an intense effort within the pharmaceutical industry to develop new and more effective therapies, particularly a class of advanced drugs known as biologics.
Among the companies at the forefront of this research is Roche, a Swiss biotech firm. Roche has been investigating a promising new drug called astegolimab, which is a type of monoclonal antibody (mAb). To understand what a monoclonal antibody is in simple terms, imagine your body's immune system producing tiny, specially shaped proteins called antibodies to fight off invaders like viruses or bacteria. A monoclonal antibody is like a factory-made version of one of these specific antibodies, designed to target a very particular part of a disease process. In the case of astegolimab, it's an investigational, fully human anti-ST2 monoclonal antibody. This means it's engineered to fit perfectly onto a specific "lock" on cells called the ST2 receptor. By binding to this receptor, astegolimab aims to block interleukin (IL)-33 signalling. Think of IL-33 as a chemical messenger that can trigger inflammation or other harmful responses in the body. By blocking its signal, astegolimab is designed to reduce the disease activity associated with COPD. Roche acquired the rights to this drug by licensing it from another company, Amgen, back in 2016.
Roche's journey with astegolimab in COPD has shown mixed results from its clinical trials, highlighting the complexities of drug development. Clinical trials are research studies conducted in humans to determine if a new treatment is safe and effective. They typically proceed through several phases.
The first key trial for astegolimab was the Phase IIb ALIENTO study, identified by the code NCT05037929. This study was a randomized trial, meaning patients were randomly assigned to receive either astegolimab or a placebo (a dummy treatment) on top of their standard care. The primary goal, or primary endpoint, of the ALIENTO study was to see if astegolimab could significantly reduce the annualised exacerbation rate (AER) at 52 weeks. In layman's terms, AER refers to the average number of times a patient experiences a serious worsening of their COPD symptoms (a "flare-up" or "exacerbation") over the course of one year. Reducing these exacerbations is a crucial goal in COPD treatment as they often lead to hospitalizations and can severely impact a patient's health. In the ALIENTO study, astegolimab successfully met its primary endpoint. Specifically, patients receiving astegolimab every two weeks showed a statistically significant 15.4% reduction in AER at 52 weeks. "Statistically significant" is an important term in clinical trials; it means that the observed reduction in exacerbations was highly unlikely to have happened by chance alone, suggesting the drug had a real effect.
Following this promising Phase IIb result, Roche advanced astegolimab into a larger, more definitive study: the Phase III ARNASA trial, identified by NCT05595642. Like ALIENTO, ARNASA was a randomized study comparing astegolimab to placebo, given on top of standard of care, which included various combinations of inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA). The patient population in both studies included individuals with severe COPD, encompassing both former and current smokers, regardless of their blood eosinophil count, and all had a history of frequent exacerbations. The primary endpoint for ARNASA was the same as ALIENTO: a significant reduction in the annualised exacerbation rate (AER) at 52 weeks.
However, despite the earlier success, the Phase III ARNASA study did not meet its primary endpoint. While astegolimab still showed a reduction in AER in ARNASA, with a 14.5% reduction also on a two-weekly dosing schedule, this result did not achieve statistical significance. This means that while there was a numerical reduction, the researchers could not confidently conclude that the reduction was due to the drug itself rather than random chance. Roche noted that the total number of exacerbations observed in the ARNASA study was lower than anticipated across both the drug and placebo groups. This unexpected low number of exacerbations might have made it harder to demonstrate a statistically significant difference between the active drug and the placebo. On a more positive note, the secondary endpoints (other measures of the drug's effect) were generally consistent in both studies, and importantly, the safety profile of astegolimab remained consistent with previous trials, with no new safety signals identified. This indicates that the drug was generally well-tolerated, which is a crucial aspect of any new medication.
Dr. Levi Garraway, Roche’s chief medical officer, acknowledged the challenges of COPD, emphasizing that it remains a leading cause of death with limited treatment options. He highlighted that these studies were groundbreaking as they included an "all-comers" COPD population, meaning they didn't exclude patients based on certain characteristics like eosinophil counts, making the findings potentially applicable to a broader range of patients. Roche plans to discuss these data with regulatory authorities to determine the next steps for astegolimab, which could involve further studies or potential submission for approval depending on the regulators' assessment.
The development of new treatments for COPD is part of a rapidly evolving landscape, often referred to as the "COPD mAb race" because of the increasing number of biologic (monoclonal antibody) therapies entering the scene. This competition is intensifying, with several therapies recently approved or showing promise in late-stage studies.
One significant development in this race was the approval of Regeneron and Sanofi’s Dupixent (dupilumab). In October 2024, the US Food and Drug Administration (FDA) approved Dupixent as the first monoclonal antibody specifically for the treatment of COPD. Dupixent has also received approval in the UK and Europe. Interestingly, Dupixent works in a similar way to astegolimab in that it targets specific chemical messengers, but instead of blocking IL-33, Dupixent blocks the signalling of IL-4 and IL-13. These are different types of interleukins also involved in inflammatory responses.
Another key player in the market is GSK’s Nucala (mepolizumab). Nucala also recently received FDA approval in May 2025 for COPD, after successfully meeting its primary endpoint in a Phase III trial in September 2024. Nucala operates with a different mechanism, as an IL-5/IL-5Rα targeting antibody. This means it targets Interleukin-5, another specific chemical messenger that plays a role in certain types of inflammation often seen in lung diseases.
It's notable that both Regeneron and Sanofi’s Dupixent, as well as GSK’s Nucala, had already received approvals for asthma before their efficacy was investigated and proven in COPD. This means these companies were able to leverage their existing research and understanding of these drugs in a related respiratory condition. Roche, however, stands out as an outlier in this trend. Unlike its competitors, astegolimab is currently more advanced in COPD trials than in asthma, indicating a primary focus on COPD for this particular drug.
The competition also includes other companies whose drugs have faced setbacks. For example, AstraZeneca’s drug, tozorakimab, which also works by blocking IL-33 (similar to astegolimab), failed to meet its primary endpoint in a Phase II study in COPD in September 2024. This highlights the high rate of attrition in drug development and the difficulty of bringing new therapies to market.
Despite the mixed results for astegolimab, the overall outlook for the COPD treatment market is positive, driven by the introduction of these new biologic therapies. GlobalData, the source of this information and a market insights platform, predicts significant growth in the COPD market across the seven major markets (7MM), which include the US, France, Germany, Italy, Spain, the UK, and Japan. GlobalData forecasts that this market will grow substantially from $11.6 billion in 2023 to $30.2 billion in 2033. This impressive growth is expected to be driven, in part, by the entry of biologics into the treatment landscape. These advanced, targeted therapies are anticipated to offer more effective options for managing COPD, potentially transforming how the disease is treated and improving outcomes for millions of patients worldwide.
COPD Researchers:
Dr. MeiLan K. Han: A Professor of Medicine and Chief of the Division of Pulmonary and Critical Care at the University of Michigan Health System. Her research focuses on understanding patient heterogeneity in COPD using techniques like thoracic CT imaging. Dr. Han is a lead investigator in major NIH-funded COPD cohort studies (SPIROMICS and COPDGene) and is the author of "Breathing Lessons: A Doctor's Guide to Lung Health". She serves on several scientific committees for organizations like the Global Obstructive Lung Disease, the COPD Foundation, and the American Lung Association, for which she also acts as a spokesperson.
Dr. Fernando J. Martinez: Currently a Professor of Medicine and Chief of the Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine. His research interests include COPD, interstitial lung disease, and lung transplantation. He has been involved in developing international guidelines for COPD diagnosis and management through the Global Initiative for Chronic Obstructive Lung Disease (GOLD). His work also involves developing personalized treatments for pulmonary fibrosis and leading a program for coordinated care of airways diseases.
Dr. Marilyn G. Foreman: Associated with Morehouse School of Medicine. Her research, including work with the COPDGene Study, has highlighted racial disparities in COPD diagnosis, noting that African Americans are often underdiagnosed due to issues with standard methods and the impact of factors like structural racism and environmental exposures. Her work advocates for more patient-centered approaches to diagnosis that consider the influence of lifelong exposures on lung health.
