Asthma and COPD Biologics: What Academic Pulmonologists See in Practice

Biologic Selection in Asthma: Phenotype, Comorbidities, and the Insurance Reality

Biologic therapy for severe asthma has matured considerably over the past decade, with 7 approved agents now targeting 4 mechanistic pathways — anti-IgE, anti-IL-4/IL-13, anti-IL-5 and anti-IL-5 receptor, and anti-TSLP — and long-term extension data confirming durable exacerbation reductions of 50% or more in appropriately phenotyped patients.1 The December 2025 FDA approval of depemokimab (Exdensur; GSK), a long-acting anti-IL-5 monoclonal antibody dosed every 6 months, further expanded the class, offering a novel dosing paradigm supported by the SWIFT-1 and SWIFT-2 trials demonstrating more than 50% annualized exacerbation reductions.2 In parallel, mucus plugging has emerged as a CT-quantifiable phenotype and mechanistically relevant biologic target: the VESTIGE trial, published in The Lancet Respiratory Medicine in 2025 and extended in AJRCCM in 2026, demonstrated that dupilumab significantly reduced airway mucus plug scores and volume over 24 weeks, with FEV₁ improvements concentrated specifically in patients with high baseline mucus plug burden.3,4 The COPD biologic landscape has similarly expanded, with dupilumab’s 2024 approval and mepolizumab’s 2025 COPD approval now offering the first 2 targeted options for eosinophilic COPD — though clinical experience suggests a therapeutic gap remains between what these agents deliver in COPD and what is achievable in asthma.5,6

Against this backdrop, HCPLive convened a panel of academic pulmonologists, physician scientists, and advanced practice providers from major US academic medical centers for a virtual roundtable on biologics in asthma and COPD. The forum was moderated by Craig Hersh, MD, a pulmonary physician at Brigham and Women’s Hospital and Harvard Medical School with clinical and research interests in COPD, alpha-1 antitrypsin deficiency, and severe asthma, and included Ben Medoff, MD, a physician investigator in lung immunology at Mass General Brigham; Chris Mosher, MD, a pulmonary critical care physician investigator at Duke University; Amy Attaway, MD, a physician scientist at Cleveland Clinic; Ash Fawzy, MD, a COPD clinical and translational researcher at Johns Hopkins; Jeong Yun, MD, a genomics-focused pulmonologist at Brigham and Women’s Hospital; Chad Wade, MD, an assistant professor studying COPD exacerbation mechanisms at the University of Alabama at Birmingham; and Danielle Wisen, PA, who runs the COPD exacerbation clinic at Cleveland Clinic’s main campus, among other participants. The panel’s composition — spanning pulmonary immunology, clinical COPD research, environmental exposures, translational genomics, and frontline APP-led COPD management — produced a discussion that moved fluidly between mechanistic nuance and the practical realities of prescribing.

The timing of the forum reflected a field where clinical experience is beginning to diverge from trial-level optimism, particularly in COPD. The GOLD 2025 and 2026 guidelines have incorporated dupilumab and mepolizumab into eosinophilic COPD escalation pathways, with distinct eosinophil thresholds — 300 cells/µL and 150 cells/µL, respectively — governing payer approval and agent selection.7 The forum also convened at a moment when the concept of asthma remission has entered mainstream clinical discourse but remains without standardized criteria or prospective outcome data.8 Against a backdrop of 7 approved asthma biologics and a growing COPD biologic evidence base, the panel addressed the clinician-level reality: which patients to treat, how to choose between agents, when to escalate to a biologic before the second exacerbation, and what to do when biologics work less well than expected.

COPD Biologics: Narrower Benefit, Tighter Insurance, and an Unmet Need for 80% of Patients

The forum’s asthma discussion converged on the recognition that while biomarkers drive the initial eligibility conversation, the practical selection among agents is shaped more by comorbidity profile, payer behavior, and patient preference than by pharmacologic differentiation. A polling question on biologic selection drivers returned biomarkers as the dominant cited factor, but open discussion quickly surfaced insurance coverage as the operative constraint: panelists described step-therapy requirements forcing mepolizumab or benralizumab before dupilumab, and patients who wanted depemokimab being required to fail other anti-IL-5s first. Dupilumab emerged as the preferred first choice for patients with concurrent atopic dermatitis, nasal polyps, or eosinophilic esophagitis, and for steroid-dependent patients given its OCS-sparing indication.

Medoff noted that tezepelumab and dupilumab are his primary asthma biologics in practice, using tezepelumab first-line for low-eosinophil patients and dupilumab preferentially for T2-high patients with comorbidities. The mucus plugging discussion surfaced as a mechanistically rich but clinically unresolved theme: VESTIGE data demonstrating that FEV₁ improvement with dupilumab is concentrated in patients with high baseline mucus plug scores generated genuine engagement, with panelists broadly acknowledging that CT-based plug scoring is not yet a clinical decision tool.3,4 As he framed the clinical and translational picture: “Clearly, people who have mucus plugs have a more severe phenotype, they’re more likely to exacerbate. So patients of mine who are frequent exacerbators, definitely with lower FEV1s, I’m getting a CT scan to look for these… there’s not strong clinical data, but there is strong basic data that removing mucus plugs may improve epithelial function. The fact that these plugs occur in the same areas over years, really implies that there is some kind of feed-forward loop there.”

The COPD discussion produced a clear and consistent finding: biologics work, but not as well or as broadly as in asthma, and the population who can access them remains limited by payer-enforced eosinophil thresholds that do not always align with clinical reality. Panelists described patients whose eosinophil counts are suppressed to 0 by steroids at the moment of measurement, forcing clinicians to rely on historical values to document TH2-high status. The panel’s practical workaround for steroid-dependent patients without documented elevated eosinophils was candidly described: coding COPD-asthma overlap as asthma-first to access the dupilumab OCS-sparing indication. Dupilumab was favored over mepolizumab across the panel based on its clinical trial performance: BOREAS and NOTUS demonstrated statistically significant FEV₁ improvements of 60 to 80 mL not replicated in mepolizumab’s METREX, METREO, or MATINEE programs.5,6 Mepolizumab retained a specific access niche — easier to approve at eosinophil counts of 150 to 300 cells/µL — despite broad acknowledgment that the evidence in patients below 300 cells/µL is limited.

Wisen described the clinical imperative in COPD as fundamentally different from asthma: “We really want to start minimizing these exacerbations sooner rather than later, just because they lose lung function every time they have an exacerbation, and they’re prone to get more exacerbations. So to break this vicious cycle, even if they’re on an ICS/LAMA/LABA and they have one flare-up after that, I’m thinking biologics.”

The single greatest unmet need, endorsed without exception by every panelist, was a therapeutic option for TH2-low COPD — estimated to represent 75% to 80% of the COPD population — for which no approved biologic exists, and for which IL-33 antagonism was identified as the most anticipated pipeline development.

References

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2025. https://ginasthma.org

2. Jackson DJ, Wechsler ME, Menzies-Gow A, et al; SWIFT-1 and SWIFT-2 Investigators. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. 2024;391(24):2337–2349. doi:10.1056/NEJMoa2406673

3. Castro M, Papi A, Porsbjerg C, et al. Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2025;13(3):208–220. doi:10.1016/S2213-2600(24)00362-X

4. Porsbjerg C, Dunican EM, Lugogo NL, et al. Effect of dupilumab on mucus burden in patients with moderate-to-severe asthma: the VESTIGE trial. Am J Respir Crit Care Med. 2026;212(2):241–252. doi:10.1164/rccm.202410-1894OC

5. 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

6. Sciurba FC, Criner GJ, Christenson SA, et al; MATINEE Investigators. Mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype. N Engl J Med. 2025;392(17):1710–1720. doi:10.1056/NEJMoa2413181

7. Global Initiative for Chronic Obstructive Lung Disease. GOLD 2026 Report. Updated 2026. https://goldcopd.org

8. Menzies-Gow A, Bafadhel M, Busse WW, et al. An expert consensus framework for asthma remission as a treatment goal. J Allergy Clin Immunol. 2020;145(3):757–765. doi:10.1016/j.jaci.2019.10.042