The therapeutic variations among patients with chronic obstructive pulmonary disease (COPD) present ongoing treatment challenges. However, the two currently approved biologics, dupilumab and mepolizumab, have shown success for a subset of patients with type 2 inflammation, and more biologics are in the pipeline for COPD, said Don D. Sin, MD, a pulmonologist at the University of British Columbia, Vancouver, Canada, in a presentation at the 2025 GOLD International COPD Conference.

Both dupilumab and mepolizumab were originally approved for asthma but were subsequently studied in patients with COPD who continue to experience symptoms and moderate-to-severe exacerbations despite other treatments and who demonstrate type 2 inflammation based on high blood eosinophil counts, Sin said. The biologics target inflammatory pathways to get to the root of the problem, he added.

Dupilumab works by inhibiting the actions of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation. In the BOREAS trial, which supported dupilumab’s approval, patients treated with dupilumab showed a 30% reduction in moderate-to-severe exacerbations compared to a placebo, along with improvements in forced expiratory volume per second and quality of life. The findings were confirmed in the subsequent NOTUS study, Sin said in his presentation.

For mepolizumab, data from a 2024 study showed the greatest benefits for both asthma and COPD in patients with the highest blood eosinophil levels (500 cells/µL or higher). In the MATINEE study, which contributed to the drug’s regulatory approval for COPD, mepolizumab was associated with a significantly shorter time to the first exacerbation and a reduced frequency of subsequent exacerbations compared to placebo. 

Sin noted the airway remodeling that occurs in asthma and COPD. At the cellular level, bronchoalveolar lavage eosinophils, but not blood eosinophils, predict exacerbations and are related to type 2 inflammation, Sin said in his presentation.

Both dupilumab and mepolizumab target IL-4 and IL-13; other biologics in development that target other pathways have shown less success, said Sin. Phase 3 studies of astegolimab, benralizumab, and itepekemab have fallen short of expectations for COPD patients, he said.

In clinical practice, patient selection is key for successful use of biologics, Sin said. For biologics, the ideal patients with COPD are those who have maxed out standard inhaled therapies and continue to suffer multiple moderate-to-severe exacerbations. Some patients with COPD experience persistent exacerbations because they continue smoking or fail to use their prescribed inhalers; these patients would not be good candidates for biologics.

A better understanding is needed of the many causes and faces of COPD in order to manage the heterogeneity of the disease and optimize the use of biologics, Sin emphasized. He noted that COPD may be caused by genetic and/or a range of outside factors, including early life events, environmental exposures, infection, or smoking, including secondhand smoke. More research is needed to identify prognostic markers and markers to predict drug sensitivity and resistance, he added.

Benefits for Challenging Cases

The use of dupilumab or mepolizumab may help increase the time to the next moderate or severe exacerbation, improve quality of life, and improve lung function for patients with COPD who have frequent or severe exacerbations despite being on maximal inhaled triple therapy, said Gerard Criner, MD, chair and professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia. 

These approved biologics may also decrease the need for hospitalization or emergency department admission or shorten ICU stays for patients, said Criner, who also serves as director of the Temple Lung Center. 

“Some factors that have been helpful in the clinical trials studying both of these agents include the presence or absence of chronic bronchitis, the presence of elevated FeNO [fractional exhaled nitric oxide], the severity of airflow obstruction, a prior history of severe exacerbation, and the level of impairment in their quality of life,” Criner told Medscape Medical News.

Looking ahead, more research is needed to assess biologics in a community population that usually is more ill and has more comorbid conditions in order to further inform the efficacy and safety of these products, Criner added.

Sin disclosed receiving honoraria from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim for COPD talks, but not for his presentation at the GOLD conference. He also reported receiving a grant to his institution from Nextone and disclosed serving as deputy chief editor of the European Respiratory Journal. Criner disclosed serving on a data safety monitoring board for dupilumab studies and as an investigator on mepolizumab trials.