Biologics in Asthma and COPD: Real-World Gaps, Outcomes, and Unmet Needs

The biologic landscape for obstructive airway disease has expanded markedly over the past decade, with 7 agents now approved for asthma across 4 mechanistic targets — anti-IgE (omalizumab), anti-IL-4/IL-13 (dupilumab), anti-IL-5 and anti-IL-5 receptor (mepolizumab, benralizumab, reslizumab, and depemokimab), and anti-TSLP (tezepelumab) — and 2 agents approved for eosinophilic COPD, with clinical trial evidence supporting exacerbation reductions of 18% to 70% across the approved indications.¹

In asthma, long-term extension data now demonstrate durable efficacy: the TRAVERSE study showed annualized exacerbation rates remaining low through week 96 of dupilumab treatment, with 75% to 90% reduction in oral corticosteroid (OCS) exposure in OCS-dependent patients who originally received placebo in VENTURE, while COLUMBA confirmed a 56% exacerbation reduction over a mean 3.5 years of mepolizumab treatment.²,³ The December 2025 approval of depemokimab (Exdensur; GSK) — the first biologic in any class dosed every 6 months — marked the latest expansion of the asthma armamentarium, with SWIFT-1 and SWIFT-2 demonstrating 58% and 48% annualized exacerbation reductions, respectively.⁴ In chronic obstructive pulmonary disease (COPD), dupilumab's BOREAS and NOTUS trials demonstrated 30% to 34% exacerbation reductions — alongside a distinctive FEV1 improvement of 62 to 83 mL not observed with mepolizumab — while the METREX, METREO, and MATINEE program placed mepolizumab in the GOLD guidelines at a blood eosinophil threshold of 150 cells/µL, lower than dupilumab's 300 cells/µL payer-enforced threshold.⁵,⁶

Against this backdrop, HCPLive convened a panel of pulmonologists from Pennsylvania, Georgia, and Florida for a virtual roundtable discussion on biologics in asthma and COPD. The forum was moderated by Frank Sciurba, MD, a pulmonologist with extensive COPD research expertise at University of Pittsburgh, and included peers from Jefferson Health, multi-physician private groups, a solo office-based independent practice, and a long-standing academic community practice in central Pennsylvania, as well as practices in Atlanta and Miami. The discussion spanned OCS burden thresholds for biologic escalation in asthma, biologic selection rationale, mucus plugging as an emerging endpoint, and the distinct clinical and practical landscape of COPD biologics.

MOA, Samples, Insurance, and the Mepolizumab Tachyphylaxis Signal

The panel converged on a finding that will be familiar to practicing pulmonologists: biologic selection in asthma is as often determined by what a patient can access and what samples a practice has available as by any pharmacologic reasoning. A polling question on the most important treatment driver returned nearly equal weight across biomarkers, access and logistics, and clinical phenotype — with Sciurba noting that at $80,000 per year out of pocket, any drug is "dead in the water" regardless of biomarker profile.

Within the clinical data, one panelist positioned tezepelumab and dupilumab as preferred first choices based on their broader upstream mechanism — tezepelumab targeting TSLP at the epithelium to suppress both innate and adaptive TH2 responses, and dupilumab blocking IL-4/IL-13 signaling with direct epithelial effects — compared with agents acting further downstream on IL-5 or its receptor. One panelist offered a counterpoint grounded in practical reality: initial biologic selection in her practice is driven primarily by which drug she has samples for, enabling same-visit initiation that reduces time-off-work burden and builds patient buy-in.

Outcomes across agents were described as broadly transformative in asthma: A panelist described the nasal polyp/aspirin-exacerbated respiratory disease/asthma overlap population as "extremely well" responders, and John Solick, MD, reported a patient who remained asymptomatic off omalizumab after 10 years on the drug — an anecdote consistent with published evidence supporting omalizumab disease modification.⁷ A clinically significant and novel observation emerged from Richard Friedenheim, MD, who described apparent mepolizumab tachyphylaxis in approximately 5 to 6 patients across his 12-member practice, with efficacy loss occurring at roughly 18 months prompting switches to benralizumab with improved outcomes.

Sciurba contextualized this as possibly reflecting immunogenic responses — mepolizumab turning antigenic over time and inducing an abrogating immune response, a phenomenon with published mechanistic support for this drug class — and noted that whether benralizumab shares this property is not yet established.⁸ The mechanistic distinction carries additional implications for COPD: benralizumab's complete eosinophil depletion via IL-5 receptor antagonism — as opposed to mepolizumab's anti-ligand approach, which leaves low-level eosinophils intact — has been associated with benralizumab's failure in 3 pivotal COPD trials, a paper Sciurba described as currently in peer review. His hypothesis is that complete eosinophil depletion may interact unfavorably with the neutrophilic TH1-dominant environment of COPD, potentially triggering a rebound TH1 effect and abrogating possible eosinophil contributions to viral containment — dynamics less consequential in TH2-dominant asthma.

COPD Biologics: Payer Thresholds Are Driving Agent Selection More Than Trial Data

The COPD discussion surfaced a consistent theme across practices: prescribing decisions are predominantly shaped by payer-enforced eosinophil thresholds rather than clinical preference. Mepolizumab's accessibility at blood eosinophil counts of 150 cells/µL makes it the default agent for many patients in the 150 to 300 range, despite Sciurba highlighting that the forest plot for this subgroup without a historical count above 300 shows only approximately 8% exacerbation reduction — not impressive by any clinical standard, but still the only approved option available.⁶

The panel noted that dupilumab's FEV1 improvement of 62 to 83 mL — expanding to 120 to 140 mL in patients with FeNO above 20 ppb — remains a meaningful differentiating feature absent from the mepolizumab trial program, and 1 that may be relevant to shared decision-making in patients who care about functional decline.⁵ An unpublished subgroup observation flagged by Sciurba described eosinophil variability — specifically patients with counts well above 300 at some timepoints but below at others — as among the best dupilumab COPD responders, suggesting that reactive eosinophilic response, rather than a persistently elevated threshold, may be the true pharmacologic target.

Real-world COPD outcomes were described with considerably more reserve than asthma: one panelist reported no good experience, with patients perceiving no difference, and another stated she does not have “high hopes for biologic COPD right now," reflecting a subjective success rate described by multiple panelists as substantially lower than in asthma. Sciurba challenged the outcome metrics being applied — noting that exacerbation reduction is the validated endpoint, not symptom improvement or lung function, and that patients who had 2 exacerbations instead of 3 will never know the counterfactual — but acknowledged the practical challenge of maintaining adherence in oxygen-dependent patients who feel no different.

The panel identified head-to-head asthma biologic trials, combination biologic therapy, prospective biologic holiday studies, and validated predictive biomarkers for COPD response as the most urgent research priorities — with Sciurba quoted the late Jeff Drazen: companies would "rather have X% of the market than 0% of the market if they lose a head-to-head," a structural barrier to the comparative evidence clinicians need most.

References

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

2. Wechsler ME, Menzies-Gow A, Brightling CE, et al. Evaluation of dupilumab's long-term safety and efficacy in patients with moderate-to-severe asthma: the TRAVERSE open-label extension study. Lancet Respir Med. 2022;10(1):11–25. doi:10.1016/S2213-2600(21)00322-2

3. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial [COLUMBA follow-up data]. Lancet. 2012;380(9842):651–659; Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019;143(5):1742–1751. doi:10.1016/j.jaci.2018.09.033

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6. Pavord ID, Chanez P, Criner GJ, et al; METREX and METREO Investigators. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613–1629. doi:10.1056/NEJMoa1708208

7. Ledford D, Busse W, Trzaskoma B, et al. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol. 2017;140(1):162–169. doi:10.1016/j.jaci.2016.08.053

8. 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