Highlights from ATS 2026
As one of the largest and most influential meetings in respiratory medicine, the American Thoracic Society’s 2026 International Conference (ATS 2026; 15–20 May, Orlando, FL, USA) brought together thousands of attendees across scientific, clinical, and industry communities for a week focused on the evolving future of pulmonary and critical care research.
Jessica Phillips, PSI’s Associate Director of Feasibility, shares her thoughts on the major themes at this year’s meeting, from the continued expansion of biologics and fibrosis-focused therapies, to the growing drive for increasingly precise approaches to managing patients with asthma and COPD.
Asthma: Optimizing treatment in a mature clinical landscape
Discussions at ATS 2026 shifted the biologics conversation in asthma away from proof-of-concept efficacy to optimization of treatment pathways, sequencing, and real-world effectiveness. The focus is increasingly on how these therapies perform outside of tightly-controlled trial settings, how they can be deployed across broader and more diverse patient populations, and how durable disease control can be maintained over time.
TSLP
The post-marketing PASSAGE study of tezepelumab in US patients with severe asthma [1, 2], conducted after its 2021 approval, aimed to characterize effectiveness in routine clinical practice, including in underrepresented populations typically captured in pivotal trials. Results showed a significant reduction in exacerbations across multiple asthma phenotypes, including populations traditionally less responsive to biomarker-restricted strategies. Importantly, no new safety signals were identified, reinforcing tezepelumab’s profile as a broad-acting biologic with real-world effectiveness in heterogenous (e.g., non-eosinophilic) populations.
IL-5
Results from SWIFT-1 and 2, and the AGILE open-label extension [3, 4] evaluating depemokimab in patients with eosinophilic asthma demonstrated sustained efficacy: The twice-yearly dosing being a key differentiating factor from competitors. The infrequent administration was well-received by patients and is increasingly viewed as a meaningful advantage in chronic disease management. The data support durable disease control alongside improved convenience, reinforcing a trend toward extended-interval biologics.
Treatment burden and adherence play an important role in long-term outcomes for chronic respiratory diseases. Even highly effective biologics will underperform in trials if dosing frequency, administration complexity, or patient burden lead to missed doses or discontinuation. Trials should reflect long-term (post-trial) usability and incorporate adherence and persistence as core endpoints to understand how convenience and treatment burden translate into durability of disease control.
Switching
The phase 3a NIMBLE trial explored a different (and pragmatic) clinical question – what happens when patients on an established biologic switch to depemokimab [5]? Enrolling severe asthma patients previously treated with mepolizumab or benralizumab and assessing outcomes after switching, NIMBLE reflects real-world treatment sequencing and could better serve to indicate true durable treatment effectiveness. While the study did not meet its primary endpoint for non-inferiority, secondary endpoints (including quality of life, disease control, and lung function) were generally maintained following the switch to depemokimab.
Asthma care is shifting from a question of access to a question of sequencing and treatment pathways. As biologics become widely-available, and clinically-effective across phenotypes, the challenge is not whether they work, but how to position them over time – when to initiate, how to switch, and how to sustain disease control in real-world practice. ATS 2026 highlighted how optimizing long-term pathways, rather than selecting individual agents in isolation, is now central to achieving durable outcomes.
COPD: Advanced therapy efficacy driven by biomarker-based patient selection
At ATS 2026, COPD was the major area of momentum. Biologics are no longer viewed as experimental or peripheral in COPD management; they are becoming central to the therapeutic conversation. Historically dominated by bronchodilators and symptom management, there is a definitive shift toward clearly stratified, endotype-driven treatment rather than a uniform approach. Competition is growing among novel MoAs and targeted approaches; however, the field continues to grapple with patient selection, and the challenge of replicating the strong efficacy already seen in asthma biologics.
IL-5
The strongest and most consistent signals continue to come from IL-5 inhibition, particularly with mepolizumab. Data from a pooled analysis of METREX [6], METREO [7], and MATINEE [8] demonstrated that, in eosinophilic COPD, exacerbations decreased and patients had fewer emergency room visits and hospitalizations – clear efficacy results for this subset of patients [9].
COPD is no longer being treated purely through airflow limitation severity, but rather through biologically meaningful phenotypes that can be matched to targeted therapies. In this framing, the IL-5 blockade is one of the clearest examples of successful asthma-style translation to COPD, albeit in a relatively narrow patient population.
IL-33
In contrast, results with other pathways highlight the challenges of reproducibility with COPD biologics. Itepekimab, an anti-IL-33 agent [10], demonstrated mixed outcomes across the AERIFY program at ATS 2026 [11, 12]. Both trials assessed itepekimab as an add-on in patients with COPD with a prior history of smoking:
- AERIFY-1 met its primary endpoint, showing a reduction in exacerbation rates of 27.1% (q2w dosing) and 20.5% (q4w dosing)
- AERIFY-2 did not meet its primary endpoints, and exacerbations were not adequately reduced
While the populations enrolled in both trials were similar, subtle differences – including a small current-smoker cohort in AERIFY-2 – and potential confounders including COVID-era variability, masking policies, and vaccination routes may have impacted outcomes. Despite the differences, safety was acceptable across both trials, suggesting the inconsistency lies more toward efficacy signal stability.
Taken together, the COPD biologics story is one of clear, but conditional successes. Even if the right inflammatory phenotype is suggested, the underlying complexity of translating broader immunological targets into consistent clinical benefit is likely to be an issue for sponsors in the coming years. COPD is a dual reality: Biologics can work, but only when paired with robust biomarker-driven patient selection.
Interstitial lung diseases: Cautious optimism in IPF
Currently-approved treatments for IPF (e.g., nintedanib, pirfenidone) slow disease progression but do not reverse established fibrosis. At ATS 2026, there was continued momentum around novel antifibrotics and expansion of treatment into broader fibrotic phenotypes.
Treprostinil
After demonstrating anti-fibrotic properties in a post-hoc analysis of the INCREASE study of pulmonary hypertension, treprostinil was evaluated in two phase 3 studies (TETON-1 and TETON-2) in almost 1,200 patients with IPF [13, 14].
TETON-1 data was presented at ATS 2026; the primary and secondary endpoints were met, with treprostinil demonstrating statistically significant improvements in both placebo-corrected difference in FVC at 52 weeks, and percentage change in predicted FVC. Benefits extended beyond FVC, with reduction in clinical worsening, improvements in time to first acute exacerbation, and overall survival were also demonstrated. Treatment effects were seen in multiple subgroups of patients (e.g., those receiving/not receiving background therapy).
A pooled analysis across both TETON-1 and TETON-2 showed robustness of results, with reduction in clinical worsening and acute IPF exacerbation also observed, suggesting a potential disease-modifying effect.
Realizing the impact of the TETON-1 and TETON-2 studies required a long duration (up to 52 weeks). This highlights a persistent challenge in IPF – endpoints require extended observation to generate meaningful data. For sponsors, smart IPF study design is needed to balance the trade-off between generating robust, clinically-meaningful evidence and meeting operational and development timelines. If regulatory review is successful, treprostinil would represent the first major addition to the IPF treatment landscape in years.
Head-to-head deupirfenidone
Following encouraging data from the phase 2b ELEVATE-IPF trial where deupirfenidone was demonstrated to slow disease progression [15], the planned phase 3 SURPASS-IPF trial is in preparation for initiation [16]. This head-to-head superiority trial will compare deupirfenidone directly against pirfenidone, and if successful, would represent one of the first modern IPF registrational studies designed to demonstrate superiority over an active standard-of-care comparator. This could raise the bar for future IPF development programs and continues to reflect a broader shift toward competitive differentiation.
Buloxibutid
Unlike many other IPF drug candidates that aim to slow or prevent fibrosis, buloxibutid aims to repair lung tissue further upstream. Positive data from the AIR-IPF trial was presented at ATS 2026 [17], and the phase 2b ASPIRE-IPF trial has recently completed enrollment [18].
Positive phase 3 data is a rarity in IPF – so many promising phase 2 studies have not gone forward, despite the investigative treatment having a clear scientific rationale and early signals being positive. IPF management is moving towards combination therapy and potentially to agents with broader disease-modifying effects, so sponsors have cause for cautious optimism.
Precision medicine and targeted therapies in respiratory medicine: Final thoughts
Discussion at ATS 2026 highlighted the growing role of biologics and pathway-specific therapies, alongside increasing use of biomarkers to guide treatment selection and identify patients most likely to benefit from therapies. COPD is entering a precision-medicine era, asthma is moving beyond efficacy into pathways optimization, and cautious optimism is warranted in advancing IPF treatment.
Several strategic sponsor implications stand out from this year’s congress:
- Trial design must evolve from efficacy demonstration to decision support
- Biomarkers are becoming commercial infrastructure, not just exploratory endpoints
- Treatment burden and pathway positioning are competitive differentiators
- Reproducibility across trials will become a central regulatory and payer concern
- Respiratory disease is moving from indication-based development to ecosystem-based development
Isolated performance is no longer enough within respiratory medicine.
Contact PSI for more information on our respiratory trial support
Abbreviations
ATS, American Thoracic Society;
COPD, chronic obstructive pulmonary disease;
FVC, forced vital capacity;
IL, interleukin;
ILD, interstitial lung disease;
IPF, idiopathic pulmonary fibrosis;
TLSP, thymic stromal lymphopoietin;
References
1. Lugogo, N.L., et al., Effectiveness and Safety of Tezepelumab in a Diverse Population of US Patients with Severe Asthma: Initial Results of the PASSAGE Study. Adv Ther, 2025. 42(7): p. 3334–3353.
2. National Institutes of Health. Effectiveness and Safety Study of Tezepelumab in Adults & Adolescent Participants With Severe Asthma in the United States (PASSAGE) (NCT05329194). 2026. Accessed May 2026; Available from: https://clinicaltrials.gov/study/NCT05329194.
3. Wechsler, M., et al., Long-Term Safety and Efficacy of Depemokimab in Patients with Type 2 Asthma: A Single-Arm, Open-Label Extension Study (AGILE). Journal of Allergy and Clinical Immunology, 2026. 157(2): p. AB278.
4. Jackson, D.J., et al., Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. N Engl J Med, 2024. 391(24): p. 2337–2349.
5. Chupp, G., et al., Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: a multicenter, randomized, double-blind, phase 3A clinical trial (NIMBLE). Am J Respir Crit Care Med, 2026. 212(5): p. 921–935.
6. National Institutes of Health. Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT02105948). 2026. Accessed May 2026; Available from: https://clinicaltrials.gov/study/NCT02105948.
7. National Institutes of Health. Efficacy and Safety of Mepolizumab as an Add-on Treatment in Chronic Obstructive Pulmonary Disease (COPD) (NCT02105961). 2026. Accessed May 2026; Available from: https://clinicaltrials.gov/study/NCT02105961.
8. National Institutes of Health. Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (MATINEE) (NCT04133909). 2026. Accessed May 2026; Available from: https://clinicaltrials.gov/study/NCT04133909.
9. Bhatt, S.P., et al., Dupilumab Versus Mepolizumab for COPD: Evaluating Efficacy Outcomes Using Placebo-Adjusted Indirect Treatment Comparison. Pulm Ther, 2026. 12(1): p. 201–217.
10. Rabe, K.F., et al., AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD. ERJ Open Res, 2024. 10(5).
11. National Institutes of Health. Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (AERIFY-1) (NCT04701983). 2026 May 2026; Available from: https://clinicaltrials.gov/study/NCT04701983.
12. National Institutes of Health. Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (AERIFY-2) (NCT04751487). 2026 May 2026; Available from: https://clinicaltrials.gov/study/NCT04751487.
13. Nathan, S.D., et al., Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med, 2026.
14. Nathan, S.D., et al., Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med, 2026.
15. Maher, T.M., et al., Deupirfenidone Compared with Pirfenidone and Placebo in Idiopathic Pulmonary Fibrosis (ELEVATE-IPF): a Phase 2b Randomized Placebo-Controlled Trial. Am J Respir Crit Care Med, 2026.
16. National Institutes of Health. Trial to Evaluate the Efficacy and Safety of LYT-100 (Deupirfenidone) Compared to Pirfenidone in Adults With Idiopathic Pulmonary Fibrosis (IPF) (SURPASS-IPF) (NCT07284602). 2026. Accessed June 2026; Available from: https://clinicaltrials.gov/study/NCT07284602.
17. National Institutes of Health. Safety, Efficacy and Pharmacokinetics of C21 in Subjects With IPF (NCT04533022). 2026. Accessed June 2026; Available from: https://clinicaltrials.gov/study/NCT04533022.
18. National Institutes of Health. A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis. (ASPIRE) (NCT06588686). 2026. Accessed June 2026; Available from: https://clinicaltrials.gov/study/NCT06588686.
