In December 2025, the FDA approved depemokimab (Exdensur) as a new add-on maintenance therapy for people ages 12 and up with certain types of severe asthma. The biologic medicine showed it could reduce asthma exacerbations (sudden worse symptoms) and hospitalizations in people with severe asthma and high levels of white blood cells called eosinophils. It also works with doses only twice each year at six-month intervals.
Drug discovery and development is a long process, and most promising drug design concepts and new drug candidates never make it all the way through. It starts with basic research to devise promising new therapeutic strategies and drug candidates. Before a new drug can ever be tested on people in clinical trials, it first has to go through lots of testing in the lab and in animal studies. Those studies examine how the drug works and whether it's likely to be safe and effective in people. Next, promising drug candidates are tested in clinical studies to find the right dose and test their effectiveness and safety. Before any drug gets approved by the FDA, studies must show that its benefits outweigh its risks for people with certain diseases or other health conditions.
Here's how that process evolved for depemokimab.
Step 1: Drug Design, Discovery, and Development
The concept for depemokimab goes back many years. Researchers wanted to find new and better ways to treat severe asthma. While most cases of asthma aren't severe, they knew that severe asthma is responsible for frequent exacerbations, hospitalizations, and health care costs. They also knew that severe asthma in some cases involves white blood cells called eosinophils and that the growth of those inflammatory cells is driven by a cytokine signaling molecule called interleukin-5 (IL-5).
Other monoclonal antibodies, or biologic medicines, targeting IL-5 or its receptor had been shown to have therapeutic benefits for severe asthma. These biologics include approved asthma medicines: benralizumab (Fasenra), mepolizumab (Nucala), and reslizumab (Cinqair). They could reduce the number of eosinophils and prevent exacerbations. They also improved lung function and quality of life in people with severe asthma and high eosinophil counts.
Most biologics require an infusion or injection every two to four weeks. But drug developers wanted to design a new antibody targeting IL-5 that would work longer, allowing people with severe asthma driven by eosinophils to receive it less often. That's where efforts to design the new IL-5-targeted biologic, now known as depemokimab (Exdensur), come in. First, drug developers used studies in yeast to tinker with and find the right chemistry. They engineered a new antibody that would bind IL-5 more strongly than those that had been developed earlier. The difference came down to four changes in the amino acids, which are the building blocks of proteins.
Step 2: Preclinical Testing in the Lab
Promising drug candidates must first get tested in the lab. They may be tested in lab dishes, cells, and animals. These tests are collectively known as preclinical studies.
To see if depemokimab might work in the way researchers had hoped, they tested it first in 16 animals. Those studies confirmed that the new monoclonal antibody targeting IL-5 at a dose of 1 milligram per kilogram (1 mg/kg) reduced eosinophil numbers for significantly longer than the same dose of mepolizumab. The findings suggested it might be possible for the biologic to work effectively in people with severe eosinophilic asthma who received it only once every six months.
Step 3: Testing in People
Once researchers see that a drug appears to work as anticipated and may be safe enough in animal studies, they can begin trying it in humans. Clinical trials are carefully designed to answer specific questions about a new drug candidate or medicine. They have to follow strict guidelines and protocols. These clinical trials typically happen in phases:
Phase 1 trials: These early trials are the first to test a drug candidate in people. They usually include 20 to 100 healthy people or people with a particular condition. They're designed to look at safety and tolerability. They also look at pharmacokinetics. Pharmacokinetics is the study of how a drug interacts in the body, including how it's absorbed, distributed, broken down or metabolized, and excreted.
The phase 1 trial of depemokimab started in December 2022. It enrolled 140 healthy people in all. The goal was to look at the new biologic's pharmacokinetics, safety, and tolerability when adults ages 18 to 50 got it under the skin using a syringe or autoinjector. They also looked at how the immune system responded to the antibody.
Phase 2 trials: Given how promising depemokimab looked and because it wasn't the first IL-5-targeted biologic, researchers were able to use a model-informed approach to further develop the new medicine. The hope was that they could get it into the clinic both safely and faster, where it could start making a difference for people with severe eosinophilic asthma. This allowed researchers involved in the drug's development to move straight from the phase 1 trial into larger, phase 3 trials to test the antibody's safety and efficacy in more people sooner than they could have otherwise.
Phase 3 trials: In February and March 2021, the first phase 3 trials testing the efficacy and safety of depemokimab, called SWIFT-1 and SWIFT-2, began. SWIFT-1 enrolled 395 adults and adolescents with severe, uncontrolled asthma and an eosinophilic phenotype. People in the study had to have persistent obstruction in their airways and a well-documented history of regular treatment with other asthma medicines. The trial excluded people with other lung conditions along with asthma, those with other conditions that increase levels of eosinophils, and those who'd had another biologic for asthma in the last 12 months. People in the study also couldn't be smokers or allergic to any other monoclonal antibody or biologic. The trial lasted for 52 weeks, or one year.
SWIFT-2 also assessed the efficacy and safety of depemokimab as an add-on therapy for severe eosinophilic asthma. It enrolled another 397 adults and adolescents. Together, the two trials represent parallel studies. They also enrolled people with severe asthma that didn't respond well to other medicines at sites all over the U.S. and the world. Meanwhile, another trial tested how well depemokimab worked compared to other biologics, benralizumab or mepolizumab.
Phase 3 trials also have tested depemokimab for patients with another condition called chronic rhinosinusitis with nasal polyps (CRSwNP). Those studies found it could improve nasal polyps and reduce nasal obstruction. While it's approved for this use in the U.K., so far, it isn't approved in the U.S. for any other indications.
Step 4: Checking by Experts
Researchers carefully analyzed the data and reported the results of the SWIFT-1 and SWIFT-2 trials in The New England Journal of Medicine in September 2024. Together, they showed that adding depemokimab to standard asthma medicines reduced the rate of asthma exacerbations each year in people with severe asthma with an eosinophilic phenotype, compared to a placebo. Any adverse events in the group who got the new biologic were similar to those in the group who got the placebo instead. A secondary analysis also showed that the new medicine led to fewer exacerbations that required a visit to the emergency room or a hospital admission.
Once a drug developer has evidence a new medicine is safe and effective, they can submit a new drug application to the FDA. An FDA review team of experts then considers all the data, including the preclinical and clinical trial evidence. The data is reviewed by a medical officer, statistician, pharmacologist, and others. They look closely to ensure the drug appears safe and effective. They also visit the study sites to confirm they have all the data and the studies were done as they should have been. The process to decide whether or not to approve a new drug can take up to 10 months.
After carefully weighing all the data to determine risks and benefits, the FDA approved depemokimab for severe asthma with an eosinophilic phenotype in December 2025. It made the biologic the first long-acting monoclonal antibody for any respiratory disease involving eosinophils and type 2 inflammation. It meant for the first time that people with this type of severe asthma could choose an add-on biologic therapy to reduce exacerbations while requiring treatment only twice a year.
Step 5: Watching Over Time
After a new drug is approved, the FDA, doctors, and drug developers continue to study it and track how safely and well it's working in patients who are taking it as indicated and prescribed. Because clinical trials include hundreds of people, not thousands, we will continue to learn more about the medicine and how well it works over time. Other clinical trials are also enrolling patients in studies testing use of depemokimab for other conditions, including hypereosinophilic syndrome and chronic obstructive pulmonary disease (COPD) with type 2 inflammation.
While depemokimab has been tested for use in treating chronic rhinosinusitis with nasal polyps and phase 3 trials suggest it may help, the FDA hasn't yet approved it for any other indication.
The Bottom Line
Depemokimab is the first ultra-long-acting biologic approved by the FDA to treat severe asthma with an eosinophilic phenotype in adults and kids 12 and up. It works by targeting interleukin-5 to reduce eosinophil counts, asthma exacerbations, emergency room visits, and hospitalizations. The FDA approved it in December 2025 based on preclinical and clinical trial results showing it's safe and effective. Unlike other available IL-5-targeted biologics approved for severe asthma such as mepolizumab, depemokimab requires treatment only twice per year.
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