Eosinophils, Exacerbations, and Endpoints: Biologic Therapy Selection in COPD and Asthma

The landscape of airway disease management has been fundamentally altered by the arrival of biologic therapies targeting type 2 (T2) inflammation. Inhaled corticosteroids, beta-agonists, and anticholinergics once defined the ceiling of what was pharmacologically possible for patients with severe asthma and COPD — but that ceiling has since shattered. Beginning with omalizumab and continuing through mepolizumab, benralizumab, and dupilumab, a wave of precision agents has reshaped how pulmonologists think about inflammatory airway disease, transforming severe asthma from a condition of symptom management to one where clinical remission is an achievable and increasingly discussed treatment goal.

The pace of that transformation has accelerated in recent years. Dupilumab's 2023 FDA approval for COPD with type 2 inflammation — the first biologic ever cleared for that indication — marked a paradigm shift in how the field approaches a disease long considered beyond the reach of precision medicine.¹ Mepolizumab followed with its own COPD approval, supported by the MATINEE trial, which demonstrated significant exacerbation reduction in patients with blood eosinophil counts of 300 cells/µL or higher.² The GOLD 2025 guidelines have now formally incorporated eosinophil counts and T2 biomarkers into the COPD escalation algorithm,³ and emerging CT-based data on mucus plug scoring are beginning to explain why dupilumab produces such striking improvements in lung function in certain patients.⁴ Meanwhile, tezepelumab — which demonstrated exacerbation reduction regardless of baseline T2 biomarker status in the NAVIGATOR trial⁵ — has challenged the eosinophil-centric framework that guided biologic prescribing for the better part of a decade. Most recently, depemokimab, an ultra-long-acting IL-5 inhibitor dosed every six months, received FDA approval for severe eosinophilic asthma,⁶ introducing a new approach to adherence in difficult-to-treat populations.

It is against this backdrop that HCPLive convened an expert forum on the Evolving Landscape of Targeted Therapy in Asthma and COPD, led by Geoffrey Chupp, MD, Professor of Medicine and director of the Asthma and Airway Disease program at Yale University. The panel included clinicians from academic medical centers and private practice across the Northeast who reviewed the clinical trial evidence base, debated biomarker thresholds, and shared candid accounts of what biologic prescribing actually looks like in busy outpatient clinics — far removed from the controlled environments of phase 3 trials.

The panel reached broad consensus on several core principles while revealing meaningful variation in individual practice. In asthma, blood eosinophils — with a preferred cutoff of ≥300 cells/μL — remain the cornerstone biomarker for biologic initiation, though FeNO and atopy testing add important nuance. Most panelists place patients on a biologic after 2 or more OCS courses per year, though Chupp and others advocated for lower thresholds in highly symptomatic patients even without documented exacerbations. Dupilumab was frequently cited as a first-line choice for patients with nasal polyps or predominant IL-13 signaling, while tezepelumab has emerged as the clear go-to agent for patients with low or absent T2 markers. Depemokimab's 6-month dosing interval generated enthusiasm for vulnerable and non-adherent populations, with panelists generally favoring a short-acting IL-5 first to confirm efficacy before transitioning. The long-term extension data for all approved biologics showed consistent durability, and newer trial data on mucus plug scores — from the VESTIGE trial with dupilumab and the CASCADE trial with tezepelumab — added a compelling radiographic dimension to understanding how these drugs drive lung function improvements.

“It's helpful to have a marker to trend in these patients to sort of see did the biologic really improve things or not. I think I have a pretty similar threshold to others and what others have mentioned in terms of actually starting a biologic. I mean, typically one course of prednisone won't do it for me. But if they're one course and they're really uncontrolled, multiple courses, like two courses, I'm definitely starting,” Sandy Zaeh, MD, MS, Pulmonary & Critical Care Medicine physician at Yale School of Medicine, said during the forum.

In COPD, the panel reflected a field still finding its footing with biologic therapy. Dupilumab was the dominant choice in practice, backed by the stronger exacerbation and lung function data from BOREAS and NOTUS, while mepolizumab's COPD uptake remained limited, hampered by comparatively modest effect sizes in MATINEE and insurance access barriers that panelists in New Jersey and other markets described vividly. Several clinicians noted that COPD patients are meaningfully harder to engage with biologic therapy than asthma patients — older, more injection-averse, and often skeptical that additional treatment can improve their quality of life. Yet those who have initiated therapy described consistently positive patient experiences, with even modest functional gains translating into meaningful improvements in daily life. The group identified long-term lung function trajectory data, clearer patient selection algorithms, and improved payer alignment as the most pressing unmet needs — and one panelist made the case bluntly: if a single avoided COPD hospitalization can offset years of biologic costs, the math on coverage restrictions is hard to defend.

References:

1. Bhatt SP, Rabe KF, Hanania NA, et al; BOREAS Investigators. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023;389(3):205-214. doi:10.1056/NEJMoa2303951

2. Eger K, Hashimoto S, Braunstahl GJ, et al. Mepolizumab for eosinophilic COPD with exacerbations (MATINEE). N Engl J Med. 2024;391(1):21-31. doi:10.1056/NEJMoa2401300

3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2025 Report. GOLD; 2025. Accessed March 11, 2026. https://goldcopd.org/2025-gold-report/

4. Dunican EM, Elicker BM, Gierada DS, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128(3):997-1009. doi:10.1172/JCI95693

5. Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med. 2021;384(19):1800-1809. doi:10.1056/NEJMoa2034975

6. Wechsler ME, Menzies-Gow A, Brightling CE, et al. Evaluation of the efficacy and safety of depemokimab in patients with severe asthma with an eosinophilic phenotype (SWIFT-1 and SWIFT-2). Lancet. 2024;404(10471):2373-2385. doi:10.1016/S0140-6736(24)02063-4