Trials Show Promise for New Agents to Treat COPD

New therapies appear to be on the horizon for chronic obstructive pulmonary disease for the first time in years. Promising results from multiple clinical trials shared at the ATS 2023 International Conference indicate a significant reduction in exacerbations, and that improvement in lung function and patient quality of life can be achieved through an injectable agent, as well as nebulized therapy.

Gerard J. Criner, MD
Gerard J. Criner, MD

“There are new targets, new therapies, that should transform the landscape for our treatment options for COPD and, more importantly, our thinking on how we should think about it,” said Gerard J. Criner, MD, chair and professor of thoracic medicine and surgery, Lewis Katz School of Medicine at Temple University, and director, Temple Lung Center.

The BOREAS trial, published in the New England Journal of Medicine at the same time it was presented in the session Breaking News: Clinical Trial Results in Pulmonary Medicine, found that patients who received injections of the monoclonal antibody dupilumab every two weeks achieved all of the aforementioned outcomes.

“It is the first study to report that a targeted therapy for patients with COPD identified by a biomarker (peripheral blood eosinophil) shows significant improvement in lung function, exacerbation reduction, improvement in quality of life, and was tied to a mechanism to decrease exhaled nitric oxide, so an anti-inflammatory effect,” Dr. Criner said. “That’s important because although it’s a small subset of people with COPD, it shows there are other novel targets we could treat with patients with COPD that may be beneficial.”

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, key drivers of the inflammation present in many patients with COPD.

A second trial of this therapy, NOTUS, is underway.

David M. Mannino III, MD
David M. Mannino III, MD

“If this study replicates the findings of the first trial, this will most likely result in the first biologic therapy that is approved to treat COPD in the United States, pending approval by the U.S. Food and Drug Administration,” said David M. Mannino III, MD, professor, University of Kentucky, and medical director and co-founder, COPD Foundation.

Additional research into other pathways, including IL-33 and IL-17, is in the pipeline.

“Hopefully, we can build on this, and COPD becomes more like inflammatory bowel disease or rheumatoid arthritis, that you can go and get a specific therapy that’s based on what your endotype is and be able to specifically treat the pathogenesis to change your outcome,” Dr. Criner said.

ENHANCE-1 and ENHANCE-2, also presented during the session on clinical trial results, studied the efficacy of ensifentrine, a first-in-class, dual-inhibitor of the PDE3 and PDE4 enzymes, combining a bronchodilator with non-steroidal anti-inflammatory therapy in a single compound. Patients using twice-daily nebulized therapy experienced fewer exacerbations and improved lung function.

Verona Pharma plans to submit a New Drug Application for ensifentrine to the FDA this year. If approved, it would be the first new class of therapy approved for the treatment of COPD in more than 10 years, Dr. Mannino noted.

A paper on the observational study Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease was published in JAMA at the same time it was presented at the International Conference. The study showed the prevalence of mucus plugging on CT scans and increased mortality. It was featured in the session New England Journal of Medicine and JAMA Discussion on the Edge: Reports of Recently Published Pulmonary Research.

“That is potentially another new target that should be looked at: How looking for mucus plugging, especially if artificial intelligence can be used to find mucus plugging seamlessly on imaging, might be important as a new treatment target for patients with COPD,” Dr. Criner said.

Another significant development presented at the conference was new technology that may be able to screen people before they develop an exacerbation. A group of abstracts outlined a digital wearable device used to identify exacerbations up to seven days in advance.

“That shows there is some promise using new technology to predict exacerbations in patients using non-invasive devices,” Dr. Criner said.

Don’t Miss ATS 2024 Highlights: On Demand

Don’t forget that ATS 2024 Highlights: On Demand are available to all conference registrants! On Demand will give you access to the Opening Ceremony, Plenary Session, Keynote Series, Clinical Year in Review, Adult Clinical Core Curriculum, and so much more. The topics will cover ILD, asthma, health equity, and CF, to name just a few. On Demand content will be accessible to all ATS 2024 full conference and On Demand registrants until March 2025.