Gerard Criner, MD, is chair and professor of thoracic medicine and surgery at Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center.

Gerard Criner, MD

Pegtarazimod Reduces Supplemental Oxygen Need in Hospitalized AE-COPD Patients

A phase 2 proof-of-concept trial presented at the 

American Thoracic Society (ATS) 2026 International Conference

 in Orlando, Florida, found that pegtarazimod (RLS-0071), a dual-acting anti-inflammatory peptide, reduced supplemental oxygen requirements and improved oxygenation metrics in hospitalized patients with 

, with a durable effect extending out to 60 days post-dose.

Gerard J. Criner, MD, ATSF, FCCP, FACP, from Lewis Katz School of Medicine at Temple University, presented the findings and spoke with

at ATS 2026 about what the data mean for pulmonologists managing hospitalized COPD patients.

21 patients enrolled; 10 received pegtarazimod (10 mg/kg IV TID x 3–5 days) vs 11 placebo

Reduced FiO₂ requirements sustained through 60-day follow-up in the treatment group

ROX index and O2 saturation improved vs placebo; no safety signals identified

Patients with NLR > 9 showed the greatest gains in oxygenation and respiratory rate reduction

A Persistent Gap in Acute Exacerbation Management

Hospitalized AE-COPD events carry significant clinical consequences: accelerated lung function decline, reduced quality of life, and increased mortality. Despite this burden, Criner noted that no therapies specifically targeting the acute exacerbation event have materially advanced in more than 50 years.

Neutrophilic inflammation drives the biology of acute exacerbations, and no existing therapy has proven capable of shifting outcomes for hospitalized patients. Criner said an effective therapy for neutrophilic inflammation could “change the tide” in patients admitted to the hospital.

“Pegtarazimod…which is a drug that's been used for [the] treatment of refractory chronic graft versus host disease, might uniquely fill the void to decrease neutrophilic inflammation in patients admitted to the hospital with COPD,” Criner said.

The agent inhibits the classical pathway of complement along with 2 key neutrophil inflammatory effectors—myeloperoxidase (MPO) and neutrophil elastase (NE)—positioning it as a targeted approach to the neutrophil-driven pathophysiology underlying many hospitalized AECOPD events.

The trial was a randomized, double-blind, placebo-controlled study enrolling hospitalized adults with AE-COPD. A total of 21 patients were enrolled, with 11 randomized to placebo and 10 to pegtarazimod as add-on therapy to usual care. The dosing regimen was 10 mg/kg IV 3 times daily for ≥ 3 days and up to 5 days. Participants were followed for efficacy and safety at 30 and 60 days after the final dose.

Primary oxygenation outcomes included change in fraction of inspired oxygen (FiO₂), oxygen saturation (O₂ sat), respiratory rate, and the ROX index, a validated calculation of SpO₂/FiO₂/respiratory rate used to predict intubation risk in acute hypoxic respiratory failure, where higher values indicate improved oxygenation and reduced work of breathing.

Compared to placebo, patients receiving pegtarazimod required less supplemental oxygen during hospitalization, as measured by decreased FiO₂, with that benefit sustained through the 60-day follow-up window. The treatment group also demonstrated increased blood oxygen saturation and improved ROX index scores relative to controls.

"Patients treated with pegtarazimod had a sooner improvement in oxygen saturation, a decrease in oxygen requirements, a slight improvement in lung function, and also an improvement in quality of life," Criner said.

No safety concerns were identified over the study period.

When patients were stratified by neutrophil-to-lymphocyte ratio (NLR), those with a high NLR—defined as > 9, consistent with strongly neutrophil-driven disease—showed the greatest respiratory benefit. This subgroup demonstrated less supplemental oxygen need, larger decreases in respiratory rate, and greater increases in the ROX index compared to patients with NLR below 9, aligning with pegtarazimod's mechanism of action.

Criner noted that while the NLR findings are based on a small sample, they are consistent with data from larger studies examining NLR as a marker of neutrophil-driven inflammation. The accessibility of NLR as a standard clinical lab value, rather than a specialized assay, could make it a practical patient selection tool if findings hold in larger trials.

Criner outlined what a definitive trial would require. A phase 2b study would need expanded enrollment, longer follow-up (a minimum of 6 months), and predefined efficacy endpoints targeting both mechanistic and clinical outcomes.

If replicated at scale, pegtarazimod could represent the first targeted anti-inflammatory strategy specifically designed for the acute hospitalized COPD setting, addressing a therapeutic gap that has persisted for half a century.

At ATS 2026, Criner also presented on pooled phase 3 data showing mepolizumab reduced COPD exacerbations and hospitalizations in patients with blood eosinophil counts starting at 150 cells/µL. Watch the interview here: 

Mepolizumab Reduced COPD Exacerbations, With Gerard Criner, MD

Editor’s note: Relevant disclosures for Criner include Pulmonx Corporation, GENZYME CORPORATION, GlaxoSmithKline, Olympus Corporation of the Americas, F. Hoffmann-La Roche AG, and AstraZeneca Pharmaceuticals.

Criner G, David J, Sadikot R, et al. Pegtarazimod (RLS-0071) Decreases Supplemental Oxygen Need in a Phase 2 Proof-of-Concept Trial in Hospitalized Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AE-COPD). Poster presented at ATS 2026 in Orlando, Florida, on May 18, 2026. 

https://ats2026.d365.events/education/sessions/b1bea76b-7dbc-4de6-ad83-8c87fba81834

Criner G. Mepolizumab Reduced COPD Exacerbations, With Gerard Criner, MD. HCPLive. Published on May 19, 2026. Accessed June 9, 2026. 

https://www.hcplive.com/view/mepolizumab-reduced-copd-exacerbations-gerard-criner-md

Videos

Phase 2 findings presented at ATS 2026 by Gerald Criner, MD, show pegtarazimod cut supplemental oxygen needs in hospitalized AE-COPD patients for up to 60 days.

Pegtarazimod Reduces Supplemental Oxygen Need in Hospitalized AE-COPD Patients 

Mepolizumab reduced exacerbations requiring emergency department visits or hospitalization among patients with eosinophilic 

chronic obstructive pulmonary disease (COPD)

 receiving inhaled triple therapy, according to pooled phase 3 findings presented at the 

2026 American Thoracic Society (ATS) International Conference

In an interview at ATS 2026, Gerard Criner, MD, from the Lewis Katz School of Medicine at Temple University, said the integrated analysis demonstrated clinically meaningful benefit across a broader range of eosinophilic COPD phenotypes than many clinicians may currently recognize. Patients with blood eosinophil counts ≥ 150 can have clinical benefit from mepolizumab.

The pooled analysis combined results from the phase 3 METREX, METREO, and MATINEE trials, evaluating mepolizumab 100 mg added to inhaled triple therapy in patients with COPD and eosinophilic inflammation.

 Across the studies, investigators analyzed outcomes among patients with blood eosinophil counts (BEC) ≥ 150 cells/µL at screening and/or ≥ 300 cells/µL in the prior year.

Among 1713 patients meeting eosinophilic criteria, mepolizumab significantly reduced the annualized rate of exacerbations requiring emergency department visits and/or hospitalization by 23% versus placebo (rate ratio, 0.77; 95% CI, 0.60-0.99; 

 =.044). The therapy also reduced the hazard of a first such exacerbation by 22% through week 104 (hazard ratio, 0.78; 95% CI, 0.62-0.97; 

 = .029). Investigators additionally observed a trend toward reduced severe exacerbations requiring hospitalization or resulting in death.

Criner emphasized that the findings reinforce the importance of recognizing type 2 inflammation in COPD and suggest that clinically relevant benefit may extend to patients with eosinophil counts beginning at 150 cells/µL.

“It shows the range of patients that have type 2 inflammation can exist at 150 and greater,” Criner said. “It means clinicians… should measure the blood eosinophil count more than once to identify a patient that… might benefit from mepolizumab.”

He noted that while some patients may not perceive substantial symptomatic improvement, prevention of hospitalization and exacerbation burden may still provide meaningful clinical benefit. Criner also highlighted the safety findings from the pooled analysis, particularly given the advanced age and comorbidity burden common in COPD populations.

Criner said decisions regarding biologic initiation in COPD should involve individualized assessment and shared decision-making discussions between clinicians and patients.

“You’re going to have to really assess the patient… and know why you’re using a biologic for them,” he said. “Is it exacerbation reduction alone? Is it trying to improve quality of life? Or is it both?”

) Mepolizumab Reduces the Burden of Chronic Obstructive Pulmonary Disease Exacerbations in a Wide Spectrum of Patients: Pooled Results From Phase III Randomized Controlled Trials. Poster presented at ATS 2026 in Orlando, Florida, on May 17.

Johnson V. Mepolizumab Reduces Type 2 COPD Exacerbations Across Variable BEC Levels. HCPLive. Published on February 28, 2026. Accessed May 19, 2026. 

https://www.hcplive.com/view/mepolizumab-reduces-type-2-copd-exacerbations-across-variable-bec-levels

At ATS 2026, pooled phase 3 data showed mepolizumab reduced COPD exacerbations and hospitalizations in patients with blood eosinophil counts starting at 150 cells/µL.

This Year in Medicine 2025 Asthma and COPD

 has been undergoing a profound transformation. What was once a field dominated by incremental adjustments to inhaled bronchodilators and corticosteroids is now moving toward a more individualized, precision-medicine model.

Despite previous setbacks in the field such as with benralizumab (Fasenra), that shift has accelerated in 2025, driven not only by expanding biomarker research but also by the long-awaited arrival of biologic therapies for 

 approvals of dupilumab (Dupixent) for eosinophilic COPD in 2024 and mepolizumab in 2025, clinicians finally have targeted options and an expanded toolbox that reflect an increasingly nuanced understanding of disease endotypes beyond traditional silos of “

“At least in certain patients, there are mechanisms across the traditional disease categories, which, which may be flawed. It may be that our traditional names for these diseases are even fundamentally flawed. You know, there are some experts in the field who are discussing that more and more… There’s definitely food for thought in what they say,” Linda Rogers, MD, associate professor in the Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai, told 

 series, HCPLive spoke with Rogers along with Gerard Criner, MD, and Andrew (Truong-An) Ho, MD, from Temple University, to explore how biologics, biomarker-guided decision making, and new conceptual frameworks for airway disease are reshaping care today—and where the next decade of precision pulmonology may be headed.

Criner, Ho, and Rogers concur that clinicians have been moving away from rigid disease categories and lean instead into a “treatable traits” philosophy that prioritizes inflammatory patterns, biomarker profiles, exacerbation behavior, patient history, and longitudinal outcome tracking. This evolution is still in its early phases, and the field continues to grapple with operational challenges such as incomplete data sharing, fragmented care, and the wide variability in patient expectations for what optimized control looks like. But the shift is undeniable, and for many specialists, it represents the most exciting era in respiratory medicine in decades.

For much of modern respiratory medicine, asthma and COPD have been treated as distinct, siloed conditions defined primarily by symptoms, spirometry thresholds, and smoking history. Yet clinicians increasingly recognize these categorical labels often oversimplify a highly heterogeneous set of airway diseases. This is particularly true in COPD, where the past decade has revealed substantial variation in inflammatory profiles, exacerbation patterns, airway remodeling, and longitudinal progression.

All 3 experts emphasized that Type 2 (T2) inflammation—long associated with asthma—has a meaningful footprint in COPD as well. Its presence has diagnostic, prognostic, and therapeutic implications, especially now that multiple biologics are proving active across both disease spaces. The idea that a COPD patient can meaningfully respond to therapies historically approved for severe asthma has forced the field to re-examine earlier assumptions about what defines each disorder.

“This is what a clinician is going to have to decide when they see a patient, you know, is this asthma? Is this COPD? Is a COPD with overlap? And I guess the question is, does it really matter if they've they're phenotypically behaving more like COPD,” Ho, a Pulmonary and Critical Care Fellow at the Temple Lung Center, said.

Clinicians have moved away from the concept of “asthma-COPD overlap” which implies 2 fixed diseases coexisting in the same patient, in favor of viewing airway disease as a spectrum. In that model, features such as eosinophilia, fixed airflow limitation, hyperreactivity, and exacerbation susceptibility can present in various combinations, independent of which diagnostic label a patient initially receives. 

This spectrum-based framing aligns with the emerging “treatable traits” strategy clinicians have adopted: identifying which traits drive morbidity in their patients, including T2 inflammation, chronic bronchitis, emphysema distribution, exacerbation frequency, and treating them directly.

“We used to kind of think about these as 2 really separate baskets. And the more we learn, the less separate they are. There are definitely gray areas in between… The therapies that are effective in patients with asthma with eosinophils and type 2 inflammation seem to also be effective in COPD with that type of inflammation. And so, the therapies are crossing boundaries, and that is going to add a lot of value for high-risk COPD patients. We're pretty excited about that,” Rogers said.

As both asthma and COPD shift toward biological phenotyping, blood eosinophil counts have become indispensable to patient selection, risk stratification, and monitoring, especially in patients without clear separating features between asthma and COPD.

Eosinophil counts have long been considered more traditionally associated with asthma, but in practice they have become one of the most clinically actionable measures for COPD as well. However, they do not provide a full picture alone, and they can be influenced by infection, steroids, and comorbidities. Additionally, not all patients with elevated eosinophils respond to biologics, and some patients with lower counts can still exhibit T2-driven disease.

The diagnostic boundary between asthma and COPD has always been porous, but biological insights and therapeutic advances are prompting clinicians to question whether traditional labels remain fit for purpose, especially when they may fail to predict response to key therapies.

Yet moving beyond categorical diagnoses is not trivial. It impacts trial design, regulatory structures, payer policies, and the logistics of real-world practice. Even so, 2025 appears to be a tipping point: a year when novel biologic options for COPD have enabled trait-based thinking to align with therapeutic reality. 

“The lines between the 2 diagnoses are getting blurrier as more data comes out. I think there may be changes in these diagnostic boxes. It's a complicated issue because it impacts sort of how the criteria for designing clinical trials and drug approval. So, it's not an easy issue to really shift on, but there's definitely movement in those spaces,” Rogers said.

Biologics Reshape the COPD Treatment Landscape

The approval of dupilumab in late 2024 as the first biologic for eosinophilic COPD marked a watershed moment in respiratory care. For more than a decade, pulmonologists had seen targeted biologics transform outcomes in severe asthma, with patients who needed chronic prednisone, or had multiple annual exacerbations, suddenly able to dramatically reduce flares, improve symptoms, and in some cases even achieve clinical remission.

COPD clinicians, dealing with a condition historically defined by slow decline and limited therapeutic innovation, lacked equivalent tools. The arrival of dupilumab—and soon after, mepolizumab—changed that calculus as the first targeted biologic option for COPD, one that offered hope to a subset of patients who had exhausted traditional inhaled regimens.

Although the experts note that biologics do not work for everyone, there is consensus that when they work, the responses can be striking. Patients long accustomed to multiple exacerbations per year, chronic systemic steroid use, or prolonged symptom burden may see substantial improvement once T2 inflammation is addressed directly.

Even more strikingly, subsets of patients have begun to achieve clinical remission using reasonable definitions of “no systemic steroids, no exacerbations, and good symptom control.” While remission terminology is not yet widely applied in COPD, the idea is beginning to permeate discussions—especially since the same medications are now approved in both diseases. Clinicians are beginning to wonder: if remission is possible in asthma, might it be achievable for a biologic-eligible COPD subset as well?

That question remains open, but the shift in mindset is meaningful. Many pulmonologists are moving from managing deterioration to aiming for measurable stability, flare prevention, and long-term maintenance.

Ho, Criner, and Rogers agreed that remission criteria will increasingly shape real-world care and clinical trials, particularly as more therapies targeting different inflammatory pathways enter evaluation. Biomarkers, trait-based diagnostics, early intervention, and better patient education will all be necessary to operationalize remission as a standard clinical goal.

“We'll still need some kind of bedside tool biomarker that everyone can use to define the patients better moving forward. So, I think it's still early days on patient selection, at least for COPD,” Ho said.

Real-World Implications for Clinical Decision-Making 

In practice, most clinicians already treat based primarily on traits rather than labels—particularly when faced with a patient who has a significant smoking history, fixed obstruction, and elevated eosinophils. Furthermore, what clinicians historically considered overlap may simply reflect flawed disease constructs. If T2 inflammation is driving exacerbations regardless of whether spirometry meets classic asthma criteria, does labeling meaningfully change management? Our experts think not.

“Whether they have asthma or COPD, if they have [T2 inflammation], then we're going to treat that patient with those agents that treat [T2 inflammation]. Similarly, if we have a patient with type 1 inflammation, we're going to identify and treat the patient with that… I think a lot of the classifications that have been used for disease categories in the past, they're going to become less important in the biologic pathway that needs to be treated that's causing the patient's symptoms. That's what's going to be treated,” Criner, chair and professor of thoracic medicine and surgery at Lewis Katz School of Medicine at Temple University and director of the Temple Lung Center, said.

Other hurdles include clinical trial design, which will evolve to allow inclusion of patients with mixed or ambiguous phenotypes in the near future, and regulatory frameworks, which may need to consider approvals based on trait profiles rather than diseases. 

But for now, the practical takeaway is clear: clinicians cannot rely on historical categories to guide every therapeutic decision. Biologics and biomarkers are forcing the field to accept that asthma and COPD share more pathobiology than once thought and that patient outcomes improve when therapies target what is driving disease rather than what diagnosis the chart says.

Precision Pulmonology Is Here—But Needs System-Level Reinforcement

Despite growing enthusiasm for biologics and precision medicine, major barriers still limit optimal airway disease care. Many patients underreport or forget exacerbations—especially those treated outside pulmonology—which leaves clinicians without full visibility into disease activity. At the same time, long-standing expectations that flare-ups are inevitable prevent some patients from recognizing that zero exacerbations may now be attainable with advanced therapies. Compounding these issues, many individuals reach specialty care only after years of progressive damage, underscoring the need for earlier identification of high-risk patients through better education, improved data integration, and proactive biomarker- or risk-based screening.

Our conversations with Criner, Ho, and Rogers reveal a specialty in transition. COPD is no longer managed solely through bronchodilation, smoking cessation, and palliative stabilization. With biologics now entering the treatment armamentarium, clinicians are beginning to treat COPD in a manner more akin to modern asthma care, in which inflammatory pathways dictate therapy, biomarkers guide decisions, and remission becomes an attainable target rather than an abstract ideal.

“The data we have in clinical trials [support] that there is a role for biologics in patients with COPD and [T2 inflammation]. I think the big kind of hurdle to cross is patient selection and how to really define these in the clinical setting, and which treatments to use for patients. I don't think we know that yet, and it's a little bit too early,” Ho cautioned.

This transformation requires more than new drugs. It demands broader adoption of trait-based diagnostic models, better integration between primary care and specialty care, and a concerted effort to define what good control looks like. The historical silos separating asthma and COPD management are becoming increasingly artificial, and collapsing those silos may be essential for maximizing the benefits of precision medicine.

As 2025 continues to unfold, pulmonology finds itself in a moment of convergence: biologics that transcend traditional categories, biomarkers that illuminate new pathways of risk, and clinicians who are rapidly evolving their definitions of success. The task now is to ensure that these scientific gains translate into practical, equitable, and forward-looking care for every patient with chronic airway disease.

Criner GJ, Celli BR, Brightling CE, et al. Benralizumab for the Prevention of COPD Exacerbations. N Eng J Med. 2019;381(11):1023-1034. doi: 10.1056/nejmoa1905248

Smith T. FDA Approves Dupilumab (Dupixent) for Treatment of COPD. Article. HCPLive. September 27, 2024. 

https://www.hcplive.com/view/fda-approves-dupilumab-dupixent-for-treatment-of-copd

Johnson V. FDA Approves Mepolizumab for Eosinophilic COPD. Article. HCPLive. May 22, 2025. 

https://www.hcplive.com/view/fda-approves-mepolizumab-for-eosinophilic-copd

Articles

Pulmonology is transitioning towards precision medicine, driven by biomarker research and biologic therapies for COPD. Recent FDA approvals of dupilumab and mepolizumab have expanded treatment options, challenging traditional asthma and COPD categorizations. Experts advocate for a "treatable traits" approach, focusing on inflammatory patterns and biomarker profiles. This shift necessitates rethinking diagnostic labels and trial designs. Despite challenges like data sharing and patient expectations, the integration of biologics and biomarkers is reshaping care, aiming for stability and remission in airway diseases.

Discover how precision medicine reshapes COPD treatment, focusing on inflammation and patient-specific traits for improved outcomes in airway diseases.

Rewriting Airway Disease With Trait-Based Care: 2025’s Convergence of Asthma and COPD Management 

Gerard Criner, MD, spells out GOLD improvements, from interventions like smoking cessation and pulmonary rehabilitation to the heightened importance of spirometry for diagnosis.

Going for GOLD: Updated COPD Guidelines with Dr. Gerard Criner

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge, affecting over 14 million adults in the U.S.—with many more likely undiagnosed—and ranking as the sixth leading cause of death nationally and fourth globally. As of 2024, more than half of diagnosed U.S. patients are women, with higher prevalence seen in rural areas, and while tobacco smoking accounts for over 70% of COPD cases in high-income countries, household air pollution and occupational exposures drive a significant burden worldwide. 

Earlier this year, the GOLD (Global Initiative for Obstructive Lung Disease) guidelines, developed by a global panel of leading experts, were updated to optimize COPD diagnosis, management, and care strategies in clinical practice, including new emphases on cardiovascular disease and pulmonary hypertension in COPD.

Returning for another episode of Lungcast is Gerard Criner, MD, of Temple University, a foremost COPD expert who serves on the GOLD Board of Directors and GOLD Science Committee. In this episode, he outlines the improvements to the guidelines, from interventions like smoking cessation and pulmonary rehabilitation to the heightened importance of spirometry for diagnosis.

"The major goal of of gold is basically distill whatever information we have from clinical trials and the best epidemiologic path of physiologic evidence that we have, and make it clinically relevant for someone who's seeing patients [so] that they can adopt those recommendations," Criner said.

Lungcast is a monthly respiratory news podcast series hosted by Albert Rizzo, MD, chief medical officer of the ALA, and produced by 