COPD Biologics in Practice: Exacerbation Reduction is No Longer Enough

The story of biologic therapy in airway disease is, at its core, a story of expanding possibility — and expanding complexity. Beginning with omalizumab's approval in 2003 and accelerating dramatically over the past decade, the field has moved from a single IgE-targeting agent that required allergy consultation to a therapeutic landscape where pulmonologists now independently select among seven approved biologics spanning 5 distinct mechanisms. Mepolizumab established the IL-5 pathway as a durable target in 2015; dupilumab's dual IL-4/IL-13 blockade arrived for asthma in 2018 and redefined expectations for both lung function improvement and steroid sparing¹; and tezepelumab's 2021 approval for any eosinophil level began to challenge the biomarker-centric framework that had organized biologic prescribing since its inception.² Most recently, dupilumab's landmark 2023 FDA approval for COPD with type 2 inflammation — the first biologic ever cleared for that indication — and mepolizumab's subsequent chronic obstructive pulmonary disease (COPD) approval following the MATINEE trial³ have opened a new frontier, extending precision immunotherapy to a disease that clinicians had long assumed was beyond its reach. And with depemokimab's approval for severe eosinophilic asthma in late 2024,⁴ offering a 6-month dosing interval that reframes the adherence calculus entirely, the pace of development shows no sign of slowing.

Yet the expansion of the toolkit has not been matched by equivalent clarity about how to use it. Which biologic for which patient — and when, at what biomarker threshold, and in the face of which insurance barriers — are questions that clinical trial data can inform but cannot fully resolve. It is in that practical space that HCPLive convened a virtual expert forum moderated by MeiLan Han, MD MS, is a Professor of Medicine and Chief of the Division of Pulmonary and Critical Care at the University of Michigan Health. Together, they worked through the evidence base, traded candid assessments of which drugs they actually use and why, and confronted the practical obstacles that no trial protocol accounts for: J-code delays on newly approved agents, step therapy requirements that have pushed some panelists to stop prescribing certain biologics altogether, and the persistent challenge of patients who arrive having already accumulated a damaging history of repeat oral corticosteroid courses before a specialist ever sees them.

“I feel like the biggest issue for me, so we have 2 Urgent Cares right next to my office, and they're actually part of our healthcare system. And if patients can't get in to see me, they'll usually go see the Urgent Care, and Urgent Care hands out prednisone like candy. Like, you have a cough, here's prednisone. They have a lot much lower threshold to prescribe,” a panelist said.

Dupilumab dominated biologic selection preferences across both asthma and COPD — driven by ease of home administration, familiarity, and a perception among many panelists that it simply performs better in clinical practice than the IL-5 agents, particularly for patients with nasal polyp and eczema comorbidities. IL-5 agents retain a clear niche for very high eosinophil counts — several panelists named 600 to 800 cells/µL as the threshold where they lean toward rapid eosinophil depletion — with mepolizumab the preferred IL-5 among most, given recurring reports of end-of-cycle breakthrough symptoms with benralizumab that have led some panelists to dose it every six rather than eight weeks using office samples. Tezepelumab's positioning as a biomarker-agnostic agent has been complicated by step therapy insurance requirements and what one panelist called a "disingenuous" marketing pivot after its initial launch, though the moderator noted that 3–4 patients who failed dupilumab and benralizumab responded to tezepelumab — all non-TH2 asthma — and argued that broader familiarity with the drug is worth building. Depemokimab, meanwhile, remains more theoretical than clinical reality for most of the group, though panelists identified adherence-challenged populations — including patients who might receive a dose at hospital discharge — as compelling future use cases.

In COPD, the discussion reflected a field gaining momentum but constrained by patient expectations and payer realities. The GOLD 2025 guidelines have incorporated eosinophil counts and T2 biomarkers into the COPD escalation algorithm,⁵ and the BOREAS and NOTUS trials for dupilumab demonstrated not only exacerbation reduction but statistically significant FEV1 improvement — a finding the panel interrogated at length, with the leading hypothesis pointing to mucus plug clearance in distal airways as the likely mechanism, supported by VESTIGE trial data and an ongoing dedicated COPD mucus plug study.⁶ Mepolizumab's COPD data from MATINEE, by contrast, showed exacerbation reduction without meaningful lung function or symptom improvement,³ creating a practical differentiation that has pushed most panelists to default to dupilumab when insurance allows — and to mepolizumab only when dupilumab is denied. The core challenge in COPD that no trial has fully resolved: patients don't always feel better even when exacerbation rates decline, making biologics a harder sell than in asthma, where the "life-changing" patient report is common. Several panelists noted off-label success with dupilumab in bronchiectasis and ABPA by coding chronic obstruction and mucus plugging — and 1 panelist anecdote of a patient who came off daytime oxygen entirely after an inadvertent off-label start underscored both the drug's potential and the limits of what approved indications currently capture.

The forum closed with a look at a pipeline that promises to keep the field moving — IL-33 inhibitors with mixed trial results but ongoing third studies, tezepelumab in COPD, emerging bispecifics, brensocatib for bronchiectasis, and ensifentrine as an inhaled dual PDE3/4 inhibitor with variable but real bronchodilatory benefit — while acknowledging the fundamental gap that remains: no biomarker equivalent to the eosinophil has emerged for the neutrophilic COPD population that current biologics cannot reach. For the clinicians in this forum, that gap is not an abstraction. It is the patient on triple therapy who keeps exacerbating, whose eosinophils are normal, and for whom the next therapeutic option does not yet exist. Until it does, the panel's consensus was clear: move patients with T2 inflammation to biologics earlier, set realistic expectations in COPD, fight insurance denials aggressively, and resist the reflex to reach for prednisone when a more durable answer is increasingly within reach.

References:

1. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486-2496. doi:10.1056/NEJMoa1804092

2. 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

3. 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

4. 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

5. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD: 2025 Report. GOLD; 2025. Accessed March 17, 2026. https://goldcopd.org/2025-gold-report/

6. 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