2025 marked a turning point for chronic obstructive pulmonary disease (COPD), as years of incremental progress gave way to a more decisive shift toward targeted, biology-driven care. Long defined by symptom management and exacerbation mitigation with inhaled therapies, the field began to meaningfully embrace precision medicine, driven by regulatory milestones, pivotal trial readouts, and a growing recognition of inflammatory heterogeneity within COPD populations.

The FDA approval of mepolizumab for eosinophilic COPD anchored the year’s regulatory narrative, establishing the first IL-5–targeted biologic option for this disease and validating eosinophils as a clinically actionable biomarker. At the same time, trial results underscored both the promise and the challenges of biologics in COPD: tezepelumab failed to meet its primary endpoint, while astegolimab delivered mixed phase 3 results that highlighted the complexity of translating immunologic targets into consistent clinical benefit. Beyond biologics, advances in smoking cessation therapy, most notably with cytisinicline, reinforced the continued importance of foundational interventions alongside novel agents.

Complementing these data were broader shifts in how COPD is conceptualized and managed in practice. Updated GOLD guidelines sharpened guidance on diagnosis, comorbidities, and evidence-based care, while expert discussions increasingly emphasized trait-based approaches that blur traditional boundaries between asthma and COPD, defining 2025 as a year of recalibration for COPD that moved the field closer to personalized care while clarifying where further evidence and refinement are still needed.

FDA News

FDA Approves Mepolizumab for Eosinophilic COPD

On May 22, the FDA has approved mepolizumab (Nucala) as an add-on maintenance treatment for patients with COPD with an eosinophilic phenotype. In the phase 3 MATINEE trial, mepolizumab demonstrated a statistically significant and clinically meaningful 21% reduction in the annualized rate of moderate or severe exacerbations (0.80 events per year) compared to placebo (1.01 events per year; rate ratio, 0.79; 95% CI, 0.66 to 0.94; P = .01), successfully meeting the primary endpoint.

Data Readouts

Tezepelumab Fails Study Endpoint of Reducing Moderate-to-Severe COPD Exacerbations

Tezepelumab was not seen to reduce the annualized rate of moderate or severe COPD exacerbations, thus failing the primary endpoint of COURSE, a phase 2a trial (NCT04039113). Singh and colleagues found that the annualized rate of moderate or severe COPD exacerbations represented a nonsignificant change and thus did not meet the trial’s primary endpoint.

Genentech (Roche)’s Astegolimab Shows Mixed Data for COPD

Genentech reported mixed phase 3 results for astegolimab in COPD, with the ALIENTO trial showing a statistically significant 15.4% reduction in annualized exacerbation rate at 52 weeks, while the ARNASA trial failed to meet its primary endpoint despite a similar 14.5% reduction. Neither trial found no new safety signals, but the inconsistent efficacy results may challenge astegolimab’s regulatory path.

Cytisinicline Demonstrates Value as Smoking Cessation Tool in People With or Without COPD

A post-hoc analysis of the phase 3 ORCA-2 and ORCA-3 trials found that cytisinicline significantly increased smoking abstinence rates compared with placebo in both COPD and non-COPD subgroups. In participants with COPD, quit rates reached 17.3%–19.1% with cytisinicline versus 2.1% with placebo, while non-COPD participants achieved 19.3%–32.6% compared to 5.5%–8.6% with placebo. The therapy was well tolerated, with insomnia and headache as the most common adverse events, supporting its potential as a safe and effective smoking cessation option.

Features and Podcasts

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

Pulmonology is rapidly shifting from rigid disease labels toward a precision, trait-based model, fueled by biomarker insights and the arrival of biologics for COPD. In this This Year in Medicine feature, leading experts discuss how approvals of dupilumab and mepolizumab are blurring the asthma–COPD divide and redefining airway disease management around inflammatory drivers rather than diagnostic silos.

Going for GOLD: Updated COPD Guidelines with Gerard Criner, MD

COPD continues to pose a substantial global and US health burden, prompting updated 2024 GOLD guidelines that sharpen guidance on diagnosis, comorbidity management, and evidence-based care. In this Lungcast episode, Gerard Criner, MD, breaks down key updates, including renewed emphasis on spirometry, smoking cessation, pulmonary rehabilitation, and cardiovascular risk, highlighting how GOLD translates evolving science into practical, patient-centered recommendations.

The Biologic Era in COPD: What Mepolizumab Approval Means for Exacerbation Control
In this HCPLive expert discussion moderated by Joseph Khabbaza, MD, clinicians examine how the FDA approval of mepolizumab for eosinophilic COPD could mark a turning point in a field long limited to symptom-focused therapies. Drawing on phase 3 MATINEE data, the panel highlights its potential to reduce exacerbations, limit systemic steroid exposure, and usher COPD care toward a more asthma-like, biomarker-driven precision model.

References

1. Johnson V. FDA Approves Mepolizumab for Eosinophilic COPD. Article. HCPLive. May 22, 2025. https://www.hcplive.com/view/fda-approves-mepolizumab-for-eosinophilic-copd

2. Johnson V. Tezepelumab Fails Study Endpoint of Reducing Moderate-to-Severe COPD Exacerbations. Article. HCPLive. January 24, 2025. https://www.hcplive.com/view/tezepelumab-fails-study-endpoint-reducing-moderate-to-severe-copd-exacerbations

3. Johnson V. Genentech (Roche)’s Astegolimab Shows Mixed Data for COPD. Article. HCPLive. July 21, 2025. https://www.hcplive.com/view/genentech-roche-s-astegolimab-shows-mixed-data-for-copd

4. Johnson V. Cytisinicline Demonstrates Value as Smoking Cessation Tool in People With or Without COPD. Article. HCPLive. September 22, 2025. https://www.hcplive.com/view/cytisinicline-demonstrates-value-smoking-cessation-tool-with-without-copd

5. Criner G, Rogers L, Ho AT. Rewriting Airway Disease With Trait-Based Care: 2025’s Convergence of Asthma and COPD Management. Article. HCPLive. December 1, 2025. https://www.hcplive.com/view/rewriting-airway-disease-with-trait-based-care-convergence-asthma-copd-management

6. Rizzo A, Criner G. Going for GOLD: Updated COPD Guidelines with Gerard Criner, MD. Video. HCPLive. May 29, 2025. https://www.hcplive.com/view/going-for-gold-updated-copd-guidelines-with-gerard-criner-md

7. Khabbaza J, Desai NS, Costanzo E. The Biologic Era in COPD: What Mepolizumab Approval Means for Exacerbation Control. Video. HCPLive. July 30, 2025. https://www.hcplive.com/view/biologic-era-copd-mepolizumab-exacerbation-control