New Treatment for COPD: An Expert's Insights and Key Facts

5 min read

By David M. Mannino III, MD, with Rachel Reiff Ellis

David Mannino is co-founder and chief medical officer of the COPD Foundation. He's an internal medicine doctor with a specialty in pulmonary, critical care, and sleep medicine at University of Kentucky Health Care. Formerly, Mannino served as chief science officer of the CDC's Air Pollution and Respiratory Health Branch, where he was lead author on key publications reporting on the causes, spread, and control of COPD and asthma. He has over 300 related publications in leading peer-reviewed journals.

The insights shared here represent his knowledge as a medical professional.

Chronic pulmonary obstructive disease (COPD) is a long-lasting condition that damages tissue in your airways, causing inflammation. This reduces your lung function and makes it harder to breathe because of what we call "obstructive airways."

In the U.S., as in most high-income countries, the most common risk factor is cigarette smoking. But it's not the only risk factor. We see it related also to occupational exposures and respiratory infections early in life. People who have had a lifelong history of asthma, often even in the absence of smoking, can develop COPD. And in a proportion of the population, it's going to be genetic.

In May 2025, the FDA approved mepolizumab (Nucala) for treatment of COPD. Mepolizumab is the second of a relatively newer class of therapies called biologic treatments to be approved for COPD.

Mepolizumab as a therapy has been around for about 15 years. At first, it was proposed as a treatment for severe asthma. When researchers were developing it for this use, the early trials failed because it didn't work in everybody with severe asthma. But when researchers looked at their early data further, they found a subset of patients who had done particularly well with this therapy.

 They then devised clinical trials to look at that subset of patients and found that they had a marked reduction in both their exacerbations (sudden flare-ups of severe symptoms) and their need for systemic steroids. That's how they discovered the therapy worked best for people with high levels of specific markers for allergy called eosinophils.

 There was a similar approach in COPD. Through clinical trials, researchers discovered enough evidence that even in the absence of asthma, for people with elevated eosinophils, mepolizumab could be a helpful treatment.

Although we give this condition the umbrella term of COPD, there are different types, or subcategories.

Mepolizumab's label specifies that this treatment is for people with the eosinophilic phenotype of COPD. This represents about 20% to 40% of all people with COPD. These are the specific people for whom mepolizumab has demonstrated a benefit. 

Up until 30 years ago, virtually all the therapies that came on the market for COPD were small molecule drugs [those with molecules small enough to easily cross cell membranes]. They were often derivatives of naturally developed products. Then, scientists started introducing biologic drugs as a different type of treatment for COPD. Biologics were developed as therapy that takes advantage of the way our immune system creates antibodies to certain bacteria and other products. Biologics are targeted therapies that focus on a very specific pathway.

In September 2024, the FDA approved the first biologic – dupilumab (Dupixent) – for the treatment of COPD. Now we have a second biologic treatment option, mepolizumab.

Dupilumab and mepolizumab target different inflammatory pathways in the body. Dupilumab targets and blocks proteins called interleukin 4 (IL-4) and interleukin 13 (IL-13). Mepolizumab targets interleukin 5 (IL-5), which is a part of the immune system that is activated in allergic reactions.

Mepolizumab was approved based on its ability to decrease exacerbations in patients with an eosinophilic phenotype of COPD. In clinical trials, people on mepolizumab had a reduction in flare-ups of 30% to 35%.

 I always tell my patients that our ultimate goal for exacerbations is zero. But there is still value in reducing them by 30% to 35%. Each exacerbation has the potential to put you in the hospital, and these visits can increase mortality. So anything we can do to reduce exacerbations at all is helpful.

 It is possible for some people not to respond to anything. That's the unfortunate reality of a progressive chronic disease. But also, if you haven't responded to one biologic therapy, it doesn't mean that you won't respond to a different one.

You take mepolizumab as an injection under the skin once a month. Your doctor will give you the first injection in the office. After that, you can give them to yourself at home with a self-injecting formulation.

The most common side effect is a reaction at the site of your injection. Some people get a sore arm related to that. But there can be more serious side effects in people who have a hypersensitivity or allergic reaction to the injection itself.

That serious injection site reaction is very rare, but it's typically why the first injection happens under the supervision of a doctor – so they can watch for symptoms like swelling of the mouth, breathing issues, feeling lightheaded, or hives. If you don't have these symptoms after the first injection, you can give yourself the rest of the injections at home.

As with most drugs, there are warnings related to pregnancy and breastfeeding. That's not typically an issue in the COPD population, but there's always that potential. The drug also targets the same part of the immune system that helps fight parasitic infections, so you'll need to take that into consideration if you're taking mepolizumab in parts of the world where that's a concern.

Also, if you're on oral or inhaled steroid medications, you shouldn't stop those while taking mepolizumab without the guidance of your doctor. If it looks like treatment is working, there may be an opportunity to decrease the systemic corticosteroids.

Biologic therapies are more expensive than other therapies we have out there, and typically too expensive for people to afford out of pocket. Because insurance companies are the ones that pay for the bulk of these therapies, they tend to withhold coverage unless someone has tried less expensive therapies first.

At the University of Kentucky, we have a pharmacist in our clinic whose main job is to help people gain access to these therapies. They work to demonstrate what therapies someone is currently on, how they are not working for them, why they would benefit from the therapy, and to be sure that they meet the various criteria that insurers have set.