In May 2025, the FDA approved mepolizumab (Nucala) as a treatment for chronic obstructive pulmonary disease (COPD). Before any drug gets near a pharmacy shelf, it starts with years of basic science research. The FDA approval process for any new treatment is involved and careful, and requires testing in a lab, then testing in real people to be sure it's safe and effective.
This testing allows researchers to more accurately say how well the drug works and answer questions such as: Do certain groups of patients benefit more from it than others? Are there any safety risks or concerns? The FDA uses the information from these trials to decide whether to approve the drug.
Here's how that process evolved for mepolizumab.
Step 1: Discovery and Development
Mepolizumab first appeared on the medical treatment scene nearly 10 years ago as a biologic drug that doctors could prescribe for severe asthma. Biologics are drugs that researchers make in a lab that mimic biological chemicals in your body and either enhance or block the effect of that chemical.
Mepolizumab blocks a chemical in your body called interleukin 5 (IL-5). IL-5 plays a key role in a specific type of inflammation – type 2 or TH2 inflammation – that results in higher levels of white blood cells called eosinophils. Eosinophils play a role in the body's immune response, especially in defending against parasites and allergens (substances that cause allergic reactions).
"The simple thought was that if we blocked interleukin 5, which causes these eosinophils to rise and results in these inflammatory pathways, we could stop disease activity," says Frank Sciurba, MD, a pulmonologist and director of the Emphysema/COPD Research Center at the University of Pittsburgh Medical Center.
With this idea in mind, researchers got to work conducting clinical trials for asthma. The FDA approved it to treat severe asthma (eosinophilic asthma) in 2015, and later for eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, and chronic rhinosinusitis with nasal polyps. COPD is the fifth condition the FDA has approved mepolizumab to treat.
Step 2: Testing in the Lab
This step of the process involves giving the drug to animals in a laboratory. Researchers did this in the early studies of mepolizumab for asthma, so animal testing didn't have to be done again for the FDA to approve it for treating COPD.
Instead, researchers were able to move directly to later phases of clinical trials in humans.
Step 3: Testing in People
Once researchers see that a drug is safe to use in animals, they begin trying it in humans. These clinical trials typically happen in phases:
Phase I trials: Researchers use a small group of people (fewer than 100) to try the drug in humans for the first time. "Phase I trials are often just purely safety trials," says Sciurba. "These are eyes-wide-open, generally healthy volunteers that get paid just to see that they're safe."
Phase II trials: The new drug or treatment is given to a larger group of people (100 to 300) to see if it works to treat the condition and look further at its safety. Researchers also work to figure out what dose of the drug makes the most sense.
"It's the Goldilocks concept, especially in immune suppression," says Sciurba. "You have to hit the sweet spot. You don't want to suppress any more than you have to, but if you don't do it to some degree, you're not going to get the effect to get rid of these harmful pathways."
Phase III trials: The new drug or treatment is given to large groups of people (1,000 to 3,000) to further show that it's effective, watch for side effects, and compare it to other treatments.
Researchers knew that mepolizumab wouldn't be an effective treatment for every person with COPD. Only 20% to 40% of people living with COPD have the specific type of airway inflammation that mepolizumab addresses.
"Mepolizumab is only tackling that subset of COPD – the bronchitis component that is being driven by eosinophilic inflammation," says Mario Castro, MD, MPH, principal investigator for the Kansas City site of the American Lung Association Asthma Clinical Research Centers (ACRC).
Step 4: Checking by Experts
Two phase III trials were important to the approval of mepolizumab. The first, METREX, tested the drug on 836 people in 2017. But the FDA ruled that this trial didn't show enough efficacy to approve mepolizumab to treat COPD. This "failure" helped researchers learn an important piece of information about whom the drug would work best for.
"The most important mechanism of the drug is to prevent the activity of the eosinophils, and decrease the ability to attract eosinophils to areas of inflammation, so the higher the eosinophil level, the more likely that the drug is going to work," says Sciurba.
This led to a phase III pivotal study called MATINEE. Researchers specifically recruited subjects with eosinophilic COPD who had an eosinophil count of 300 or greater.
"In response to treatment with mepolizumab over a year, that population had a 20% decrease in exacerbations of their COPD," says Castro, who's also the division chief of pulmonary, critical care, and sleep medicine at the University of Kansas Health System.
This outcome earned mepolizumab an FDA approval for treating COPD.
Step 5: Watching Over Time
After a drug is approved by the FDA and doctors can prescribe it to people, researchers continue to track its safety and make sure it's working as effectively as possible. Because clinical trials are a relatively small subset of all people with the condition the drug treats, this helps them see how the results look in much bigger groups of people.
"Clinical trials typically have under a thousand people in them, so when you scale it up to 30,000 to 50,000 people, more rare events that could be causally related may start to peek out," says Sciurba. "So always there should be a level of observation, whether it's by the FDA or the medical community in general, to continue to monitor any therapies."
The Bottom Line
Mepolizumab is the second biologic the FDA has approved for treating COPD. The first, dupilumab (Dupixent), works in a similar way but targets different chemicals: IL-13 and IL-[1] 4. The FDA approved dupilumab for COPD in September 2024. Both drugs are very safe and well tolerated, and are only the tip of the iceberg, says Castro.
"[The people who qualify for mepolizumab] represent a small proportion of patients with COPD," he says. "We still have a lot of work to do, because the other people with COPD need these treatments. But this is an exciting start."
