New COPD Treatment Approvals and the Pipeline Behind Them

For a very long time, treating chronic obstructive pulmonary disease meant choosing among different versions of the same basic tool. A 2019 review published in a PMC journal on COPD drug development noted that despite a wide range of treatment options, nearly all of them were iterations of bronchodilators, medications that relax and open the airways, with only one genuinely novel drug class approved in the prior 25 years. That is the backdrop against which a cluster of new approvals and a fast-moving pipeline now stand out.

Two new biologic drugs have reached FDA approval in COPD by targeting the inflammation itself rather than just the airway muscle, and a third new inhaled drug works through a completely different mechanism than anything approved in decades. Behind those approvals sits a pipeline that includes drugs that failed to hit their goals, drugs being tested in new ways, and early regenerative approaches aimed at repairing lung tissue rather than managing symptoms around it. Here is what has actually been approved, what the trial data shows, and what is still investigational.

Why COPD Treatment Has Stalled for Decades

COPD affects more than 390 million people worldwide and ranks as the third leading cause of death globally, according to GSK's announcement of its FDA approval for Nucala. For most of that population, the available treatments have not changed in kind, only in combination and delivery. The PMC review on COPD drug development put it plainly: only one novel drug class having been approved in the last 25 years, with the rest of the pharmacy largely made up of bronchodilator iterations that open airways without changing the disease process underneath them.

That stagnation matters because COPD is not static once it is diagnosed. It is a progressive disease, and bronchodilators, while genuinely useful for symptom control, were never designed to stop that progression. The arrival of a new drug class, biologics that interrupt specific inflammatory signals, represents the first real departure from that pattern in a generation. It does not mean COPD is solved. It means there is now more than one lever to pull, and that matters given the scale of the disease and its cost: emergency department visits and inpatient care for COPD already cost the US healthcare system around $7 billion a year, according to GSK.

New FDA-Approved Biologic Add-On Therapies for COPD

Both of the newly approved biologics are designed to be added on top of existing treatment, not to replace it. The standard of care for most people with COPD remains triple inhaled therapy, a combination of three inhaled medications that relax airway muscles and reduce general inflammation. The new biologics step in when that standard regimen is not enough, specifically for patients who keep having exacerbations, flare-ups of symptoms that often require extra medication or hospital care, despite being on triple therapy. Rather than working through airway muscle relaxation, these biologics target type 2 inflammation, a specific inflammatory pathway driven by immune cells called eosinophils.

Mepolizumab Nucala Approval and Eligibility

The FDA approved Nucala (mepolizumab) as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype, a subtype of the disease marked by elevated eosinophils in the blood. GSK's approval announcement states that the decision was based on data from two positive phase III trials, MATINEE and METREX.

MATINEE assessed mepolizumab over 52 to 104 weeks in 804 patients with COPD who had a blood eosinophil count of at least 300 cells per microliter, and it produced a statistically significant rate ratio of 0.79 compared with placebo. METREX evaluated the drug over 52 weeks in 836 patients, split between an eosinophilic phenotype group and a non-eosinophilic group, and showed a statistically significant rate ratio of 0.82 in the eosinophilic group. Both trials used the same primary measure: the reduction in the annualized rate of moderate or severe exacerbations, meaning how often, on average per year, a patient's symptoms worsened enough to need extra treatment.

One detail sets Nucala apart from other biologics evaluated in COPD. According to GSK, it is the only approved biologic that has been evaluated down to a blood eosinophil count threshold as low as 150 cells per microliter, lower than the 300 cell threshold used to enroll patients in MATINEE. That lower bar matters in practice, because about 70% of people whose COPD is inadequately controlled on triple therapy have a blood eosinophil count of at least 150 cells per microliter, per GSK, which puts a large share of that population within reach of this treatment. The most common side effects reported in Nucala's prescribing information are back pain, diarrhea, and cough. As of this approval, mepolizumab is not yet approved for COPD outside the United States, with regulatory submissions still under review in the European Union and China.

Dupilumab Dupixent Trial Results and Approval

Dupilumab (marketed as Dupixent) took a different route to the same goal. The NOTUS trial, a randomized, double-blind phase 3 study, compared dupilumab with placebo in adults with moderate or severe COPD and evidence of type 2 inflammation. After 52 weeks of treatment, the annualized rate of moderate or severe exacerbations was 34% lower in the dupilumab group than in the placebo group, according to reporting from the American Thoracic Society conference news coverage of the trial results.

That confirmed an earlier signal. In March 2023, Sanofi and Regeneron announced positive results from an earlier phase III trial showing that Dupixent reduced COPD exacerbations by 30% and improved lung function, according to coverage in Applied Clinical Trials Online. The NOTUS results, reported later at 34%, line up with and extend that earlier finding.

Mechanistically, dupilumab takes a different path than mepolizumab even though both are aimed at type 2 inflammation. Dupilumab blocks signaling through interleukin-4 and interleukin-13, two proteins that drive several steps of the type 2 inflammatory response. Mepolizumab instead targets interleukin-5, a protein more specifically tied to eosinophil production and survival. Both routes lower exacerbation rates in eligible patients, but they intervene at different points in the same broad inflammatory pathway.

Ensifentrine Ohtuvayre a Nonbiologic Approval

Not every recent COPD approval is a biologic. In June 2024, the FDA approved Ohtuvayre (ensifentrine), described by FirstPointMD as the first inhaled product in more than two decades to work through a genuinely novel mechanism. Ensifentrine works by dual inhibition of phosphodiesterase 3 and phosphodiesterase 4, two enzymes involved in both airway smooth muscle relaxation and inflammation control. That combination lets it act on two fronts at once rather than specializing in either bronchodilation or anti-inflammatory activity alone.

The practical difference for patients is eligibility. Mepolizumab and dupilumab both require confirming an eosinophilic phenotype through a blood test before a patient qualifies. Ensifentrine's mechanism does not depend on eosinophil levels, so it does not require that phenotype testing to determine eligibility. That makes it a meaningfully different option for patients whose COPD is driven more by airway mechanics and general inflammation than by the eosinophil-driven type 2 pathway the biologics are built to treat.

Determining Eligibility for the New Biologics

Eligibility for mepolizumab and dupilumab comes down to a single lab value: blood eosinophil count, usually abbreviated BEC. It is measured with a standard blood draw, the kind a treating physician can order as part of routine bloodwork, and it reflects how many eosinophils, a type of white blood cell involved in the type 2 inflammatory response, are circulating in a patient's blood.

The threshold a patient needs to meet depends on which drug and which trial you are looking at. MATINEE enrolled patients with a BEC of at least 300 cells per microliter. Mepolizumab's approved eligibility, however, extends down to a BEC as low as 150 cells per microliter, the lowest threshold evaluated for any approved biologic in COPD, according to GSK. That distinction is not academic. About 70% of patients whose COPD is inadequately controlled on triple inhaled therapy and who keep having exacerbations have a BEC of at least 150 cells per microliter, which is the population these drugs are built to reach.

The target population for both biologics is specific: adults already on triple inhaled therapy whose disease remains inadequately controlled and who continue to experience exacerbations despite that standard regimen. A BEC test, ordered by the treating physician, is the gatekeeping step that determines whether a patient falls into the eosinophilic phenotype these drugs were designed for.

That also means roughly 30% of patients with inadequately controlled COPD, those whose BEC falls below the eosinophilic threshold, do not qualify for mepolizumab or dupilumab under their current approvals. For that group, the existing toolkit remains the relevant one: triple inhaled therapy adjustments, ensifentrine, which does not require eosinophil testing, and pulmonary rehabilitation, a structured program of exercise and education aimed at improving day-to-day function. None of this means those patients are without options, but it does mean the newest biologic add-ons are not universal.

Biologics Still in the Investigational Pipeline

Approval is not the end of the story for biologics in COPD. Several other agents aimed at eosinophils or the signaling pathways upstream of them have gone through late-stage trials without reaching the same clean result mepolizumab and dupilumab did. Two of those trials illustrate why phase III results in COPD have been harder to come by than the recent approvals might suggest.

Tezepelumab and the Nonsignificant COURSE Trial Result

The COURSE study, a phase 2a trial, randomized participants to receive tezepelumab plus triple therapy or triple therapy alone over 52 weeks, according to American Thoracic Society conference coverage. The tezepelumab group showed a 17% reduction in the annualized rate of moderate or severe exacerbations compared with triple therapy alone, but that result was not statistically significant, meaning it could plausibly have occurred by chance rather than reflecting a true drug effect.

There was a more promising signal within a subgroup: the exacerbation reduction effect was notable at a blood eosinophil threshold of 150 or greater, but the study authors noted that the trial was enriched for patients with three or more exacerbations per year, meaning the population studied was not representative of all COPD patients, and that finding needs confirmation in a larger trial before it means anything for eligibility or approval. For comparison, dupilumab's NOTUS trial produced a statistically significant 34% reduction, which underscores how far short of that bar the tezepelumab result currently falls.

A related investigational agent, astegolimab, targets upstream ST2 and IL-33 signaling, a different point in the inflammatory cascade than the IL-5 pathway mepolizumab blocks or the IL-4/IL-13 pathway dupilumab blocks, according to FirstPointMD's coverage of respiratory disease research. It remains under study and is not approved for COPD.

Benralizumab Failed Trials and the Exacerbation-Dosing Strategy

Benralizumab, which targets the IL-5 receptor alpha on eosinophils, failed to meet its primary endpoint in two phase III studies of patients with moderate to very severe COPD and a history of exacerbations, according to the PMC review of COPD drug development. As a maintenance therapy given on an ongoing basis, it simply did not separate from placebo closely enough to support approval.

A different use case produced a more encouraging result. The ABRA trial tested benralizumab not as ongoing maintenance therapy but as a single dose given at the point of an exacerbation, particularly for eosinophilic exacerbations in asthma and COPD, according to FirstPointMD. That single dose outperformed systemic steroid tablets, reducing treatment failures and improving symptoms like cough, breathlessness, and wheeze. That is a genuinely different clinical scenario than daily or monthly maintenance dosing, and it has not translated into a COPD maintenance approval for benralizumab. It is a useful finding for how exacerbations might be treated acutely, not a sign that benralizumab is close to joining mepolizumab and dupilumab as an approved add-on therapy.

Regenerative Cell Therapy in Development for COPD

Everything described so far, the biologics, ensifentrine, the drugs still failing in trials, works by suppressing inflammation or relaxing airway muscle. None of it reverses the underlying tissue damage. COPD involves progressive, irreversible destruction of lung tissue, and that destruction is what ultimately drives the breathlessness and respiratory decline that define the disease. A separate category of research is aimed specifically at that gap: regenerative approaches intended to support tissue repair rather than manage inflammation around already-damaged tissue.

SMSbiotech is developing one such approach, an investigational, nebulized, allogeneic (meaning derived from donor cells rather than the patient's own) stem cell therapy called SMS Cells, studied specifically for COPD. It is not an approved treatment, and no claims of efficacy or patient eligibility apply to it at this stage; it remains in early clinical testing. The FDA has issued a Study May Proceed notification on SMSbiotech's Investigational New Drug application, clearing the way for a US Phase 1b study. A separate Phase 1b trial is already underway in Melbourne, Australia, testing ascending doses of SMS Cells; its first cohort completed the protocol-specified 28-day safety monitoring period with no therapy-related adverse events, and dose escalation to the second of three planned cohorts is now underway. First patient dosing in the US Phase 1b study is targeted for the fourth quarter of 2026. Subject to safety and tolerability data from that Phase 1b work, a Phase 2a study is planned for the first half of 2027.

The mechanism under investigation, described in preclinical studies, involves SMS Cells binding to endogenous mesenchymal stem and progenitor cells already present in the lung and stimulating multi-gene activity associated with alveolar tissue repair, the kind of repair relevant to the air sacs damaged in COPD. That preclinical finding is distinct from, and should not be confused with, trial outcomes; it describes a proposed biological interaction observed before human testing, not a demonstrated clinical result.

Separately, basic-science researchers at the University of Pennsylvania's Perelman School of Medicine identified a new cell type in human lungs called respiratory airway secretory cells, or RASCs, according to Applied Clinical Trials Online. These cells produce proteins necessary for the mucus lining in the airways and resemble alveolar epithelial type 2 cells, which function as stem cells for the lung's air sacs and whose function is known to be impaired in people with COPD. That discovery suggests a potential role for RASCs in future treatment approaches, but it is a basic-science finding about cell biology, not a therapy currently in clinical trials, and the two should be kept separate.

What the New Approvals and Pipeline Mean for Patients Going Forward

The honest summary is that COPD treatment has genuinely expanded beyond decades of bronchodilator iteration, but none of the new options is a universal fix. Mepolizumab and dupilumab work only for patients with an eosinophilic phenotype confirmed by a blood test. Ensifentrine works through a different mechanism that does not require that testing but is not targeted at the same inflammatory pathway. Each approval solves for a specific subset of the COPD population, not the whole of it.

The pipeline behind these approvals is substantial. According to data from the WHO International Clinical Trials Registry Platform cited by Applied Clinical Trials Online, over 600 clinical trials for COPD are currently recruiting patients worldwide, spanning biologic, small molecule, device, and regenerative categories. That scale of activity reflects how much room is still left between where treatment stands today and where the unmet need remains, particularly given that COPD-related emergency department visits and inpatient care already cost the US healthcare system around $7 billion a year, according to GSK.

For patients and clinicians weighing these options, the practical task is tracking three things before assuming eligibility or availability: a patient's eosinophil phenotype status, since that determines access to mepolizumab or dupilumab; the trial phase of any investigational therapy being discussed, since phase 1b safety data and phase III approval are very different things; and whether a given therapy is actually FDA-approved or still investigational, a distinction that matters as much for regenerative approaches like SMS Cells as it does for biologics still working through late-stage trials. The new approvals are real progress. The pipeline behind them is active and worth watching, but it should be read for what it currently is rather than what it might eventually become.

References

"Multiple Trials Reflect Promise for New Methods to Treat COPD - ATSConferenceNews.org." atsconferencenews.org, https://www.atsconferencenews.org/multiple-trials-reflect-promise-for-new-methods-to-treat-copd/.

"FDA approves Nucala as add-on therapy for certain COPD patients." copdnewstoday.com, https://copdnewstoday.com/news/fda-approves-nucala-add-on-therapy-certain-copd-patients/.

"COPD: Therapies on the Cusp | Applied Clinical Trials Online." appliedclinicaltrialsonline.com, https://www.appliedclinicaltrialsonline.com/view/copd-therapies-on-the-cusp.

"Latest Advances in Treating Chronic Respiratory Diseases Like COPD and Asthma - FirstPointMD." firstpointmd.com, https://firstpointmd.com/latest-advances-in-treating-chronic-respiratory-diseases-like-copd-and-asthma/.

"Review of Drug Development Guidance to Treat Chronic Obstructive Pulmonary Disease: US and EU Perspectives - PMC." pmc.ncbi.nlm.nih.gov, https://pmc.ncbi.nlm.nih.gov/articles/PMC6896238/.

"Nucala (mepolizumab) approved by US FDA for use in adults with chronic obstructive pulmonary disease (COPD) | GSK US." us.gsk.com, https://us.gsk.com/en-us/media/press-releases/nucala-mepolizumab-approved-by-us-fda-for-use-in-adults-with-chronic-obstructive-pulmonary-disease-copd/.

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