The argument that biologics couldn’t work in COPD, that the disease was too heterogeneous, too poorly stratified, too unlike asthma, is now moot.
Three FDA approvals in under a year have closed the proof-of-concept debate in COPD biologics. The industry’s focus now is on identifying the right patient groups, meeting approval requirements, and preparing for price pressure from biosimilars.
In March 2026, AstraZeneca’s tozorakimab met the primary endpoints in the Phase III OBERON and TITANIA trials. It significantly reduced the annual rate of moderate-to-severe COPD exacerbations. A third Phase III readout in April showed similar results. IL-33 inhibition may benefit a broader COPD population. It could also expand the market beyond therapies that mainly target eosinophilic inflammation.
This study maps the COPD biologics field as it stands now: validated pathways, failed approaches, and four spaces where new positions are still open.
18 million diagnosed U.S. patients is not the biologics market
The United States has over 18 million diagnosed cases, and Japan has over 7 million. Actual prevalence is likely higher because clinicians often miss COPD, especially in women and non-smokers.
But approved biologics do not start with the full diagnosed population. They focus on eosinophilic patients who remain uncontrolled on maximal inhaled therapy. Estimates place this subgroup at 20–30% of moderate-to-severe COPD cases, depending on the eosinophil threshold.
Dupilumab set the first COPD biologics benchmark
Dupilumab reduced moderate-to-severe exacerbations by 34% in the BOREAS and NOTUS Phase III trials. Patients with elevated eosinophil counts also showed significant lung-function improvements. The FDA approved it in September 2024 for adults with uncontrolled COPD and chronic bronchitis. The EMA approved it shortly after. Since then, Dupixent’s market value has grown, projected to reach $25.7 billion by 2032, up from $14.18 billion in 2024.
In January 2026, NICE recommended dupilumab for adults with uncontrolled COPD and blood eosinophils at or above 300 cells per microliter despite maximal inhaled therapy. This recommendation serves as a benchmark for other payer systems, clarifying acceptable evidence and biomarker thresholds.
Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2026 reinforced the shift. It placed dupilumab and mepolizumab in the treatment algorithm for eosinophilic COPD patients who remain uncontrolled on triple inhaled therapy. The guidelines also lowered the exacerbation escalation threshold. A single moderate exacerbation now prompts treatment reassessment. Previously, two or more were required.
The boundary is still clear. No biologic has yet proven at-scale efficacy in non-eosinophilic COPD. That keeps the eosinophil cut-off, 150 or 300 cells per microliter, central to eligibility and reimbursement. Both drugs now sit in eosinophilic COPD. But without head-to-head data, payers and clinicians lack a clear basis for sequencing them.
Which pathways are validated, which failed, and why do they follow a single pattern
| Pathway | Company | Drug | Status | Strategic signal |
| IL-4/IL-13 | Sanofi/Regeneron | Dupilumab | FDA approved Sep 2024 | First validated COPD biologic. Eosinophil-restricted label. |
| IL-5 | GSK | Mepolizumab | FDA approved May 2025 | Confirms eosinophilic pathway. Head-to-head vs dupilumab unresolved. |
| IL-33 | AstraZeneca | Tozorakimab | Phase III complete, 3 positive readouts (Mar-Apr 2026) | Broader-label potential, pending subgroup clarity. AZ peak sales guidance: $3–5B. |
| IL-33 | Sanofi/Regeneron | Itepekimab | Mixed Phase III 2025. No filing yet. | Differentiation vs tozorakimab unclear. Mechanism overlap creates positioning risk. |
| TSLP | AZ/Amgen | Tezepelumab | Exploratory in COPD | Upstream alarmin. Rationale strengthened by tozorakimab Phase III data. |
| TNF-a, IL-1B, IL-8 | Multiple | Infliximab, canakinumab, CNTO6785, ABX-IL8 | Failed | Broad-population targeting with weak biomarker selection. A recurring failure pattern in COPD R&D. |
The failed programs share the same lesson: broad COPD populations are a poor fit for unstratified biologic development. Infliximab, canakinumab, MEDI8968, CNTO6785, and ABX-IL8 all showed weak or inconsistent efficacy. Late-stage COPD programs now need stratification built in from the start. Without it, they risk repeating the same mistake.
Omalizumab’s patent expiry showed what happens when respiratory biologic pricing opens up
Omalizumab’s patent expiry in Europe in 2025 established the first biosimilar pathway for respiratory biologics. The projected budget impact was over 641 million euros across 23 European countries over five years. Beyond cost savings, this shows how lower biologic pricing can unlock reimbursement. Health systems that could not justify the original expense may support access without new approvals or label changes.
That pricing pressure is already relevant to dupilumab, especially in markets where annual biologic costs can limit access. Respiratory biosimilars will likely expand more slowly than oncology biosimilars because COPD populations remain narrow and biomarker-gated.
Analysts project future COPD biologics will cost $35,000–$45,000 per year in the U.S. and 20–30% less in Europe. Initial launches will focus on the U.S., EU, and Japan. Market success will depend on HEOR evidence, KOL engagement, eosinophilic patient identification, and digital adherence tools. Companies entering the biosimilar space must also prioritize manufacturing consistency, physician confidence in interchangeability, and payer formulary positioning. Programs need to model biosimilar entry and evolving pricing into their 2030s plans. Without that, they risk making lifecycle decisions based on outdated market assumptions.
Four strategic spaces where the next positions are still available
1. Refined patient selection beyond eosinophil count
Eosinophil count helped open the COPD biologics market. But it is too blunt to explain non-response, mixed inflammation, or the patients who may benefit from upstream targets.
Companies can target patient groups not covered by current approvals through better biomarkers. These may include neutrophilic signatures, mixed inflammatory profiles, or mucus-related markers. Tozorakimab makes IL-33 the first real test of this wider approach.
Other pipeline assets may also support biomarker-based differentiation. These include Rademikibart, Astegolimab, Solrikitug, and Chinese biotech candidates.
2. Early biologic intervention
Current COPD biologics target moderate-to-severe patients with established exacerbation histories. That population is easier to identify, and exacerbation rate gives trials a validated endpoint. No program has yet shown whether earlier biologic use can slow irreversible airway remodeling.
GOLD 2026 lowered the escalation threshold from two moderate exacerbations to one, moving the field toward earlier treatment reassessment. Programs generating early-intervention data first may achieve clinical differentiation beyond pathway selection alone.
3. Combination biologics for overlapping inflammatory mechanisms
Many COPD patients exhibit coexisting eosinophilic and neutrophilic activity or mixed type 2 and non-type 2 inflammation. No approved therapy currently targets multiple pathways simultaneously. The rationale is clear, but the evidence burden will be high.
Programs that solve the evidence, safety, and cost case could redefine treatment for complex COPD patients.
4. Upstream inhibition before the inflammatory cascade reaches the airway
Most approved COPD biologics act on downstream mediators, such as IL-5 or the IL-4/IL-13 receptor. IL-33 and TSLP act upstream, offering potential coverage of a broader patient population. Tozorakimab suggests upstream inhibition may reach beyond eosinophil-led disease. Subgroup data will decide how broad that opportunity really is. Tezepelumab’s established efficacy in asthma through TSLP inhibition makes it a natural candidate for exploration in COPD.
Programs that establish upstream alarmin inhibition early may enter the biosimilar era from a stronger commercial position. They could differentiate through both clinical value and market timing.
Biologics will not cover the whole COPD market
Ensifentrine was approved in 2024 as the first non-bronchodilator, non-ICS inhaled therapy. It targets PDE3/4 dual inhibition. Researchers are still evaluating how it fits with existing regimens. Roflumilast continues to play a role in severe chronic bronchitis. Neither directly competes with eosinophilic COPD biologics. But both matter commercially because many COPD patients will remain outside the biologic eligibility criteria. Stem cell therapies remain early-stage and are unlikely to influence near-term strategy. For now, R&D and commercial focus will stay on biologics, inhaled therapies, and small molecules.
Building the next decade of competitive advantage
Dupilumab and mepolizumab now define eosinophil-selected COPD. IL-33 could expand the field, but only if the data holds beyond that segment.
New programs will struggle to enter the same eosinophil-defined segment. Competitive advantage will depend on sharper biomarker strategies and stronger comparative evidence. Programs also need clear value in underserved groups, including non-eosinophilic patients, earlier-stage disease, and combination therapy settings.
Large pharma companies with Phase 3 data and commercial scale are better positioned for near-term launches. Emerging biotechs may need partnerships, licensing, or targeted development paths to accelerate market entry. As dupilumab faces future exclusivity and pricing pressure, portfolio decisions must also account for biosimilars and market shifts through 2032–2035.
The strongest opportunities now sit in biomarker-led segmentation, early intervention, combination strategies, and upstream immune modulation.
GreyB helps pharma R&D teams map these white spaces, benchmark competitive positioning, and prioritize programs with the strongest clinical and commercial potential.
Explore the next whitespace in COPD biologics.
