ATS 2025: Nucala reduces COPD exacerbations, regardless of severe event history

Yahoo

20-05-2025

On May 18, at the 2025 American Thoracic Society (ATS) International Conference, updated findings from a post hoc analysis poster presentation of the Phase III MATINEE trial (NCT04133909) reinforced the efficacy of Nucala (mepolizumab) in reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype, irrespective of whether they had a history of severe exacerbations. Nucala, an anti–interleukin-5 (IL-5) monoclonal antibody developed by GSK, was associated with a sustained reduction in emergency department (ED) visits, hospitalisations, and symptom burden for up to 104 weeks in patients already receiving triple inhaled maintenance therapy.
The MATINEE trial enrolled 804 patients aged 40 years and older with COPD, a screening blood eosinophil count 300 cells/μL or higher, and a history of two or more moderate and/or one or more severe exacerbations in the 12 months before screening. Patients were randomised 1:1 to receive Nucala 100mg or placebo subcutaneously every four weeks in addition to standard triple therapy for 52–104 weeks. This analysis focused on exacerbation outcomes and symptom response stratified by the presence or absence of severe exacerbations at baseline.
Among patients with prior severe exacerbations, Nucala reduced the annualised rate of moderate/severe exacerbations by 25%. In those without a history of severe exacerbations, the reduction was 21%. The rate of exacerbations requiring ED visits and/or hospitalisation was 32% lower with Nucala in the severe and 40% lower in the non-severe subgroup. Kaplan–Meier curves demonstrated a numerically lower probability of first exacerbation requiring ED/hospital care through Week 104 in both groups (hazard ratio [HR]: 0.60 [0.34–1.05] in severe; HR: 0.70 [0.44–1.12] in non-severe).
Additionally, a greater proportion of patients treated with Nucala achieved a 4-point or greater improvement in St George's Respiratory Questionnaire (SGRQ) score compared to placebo. This improvement was more pronounced among patients without prior severe exacerbations, suggesting that early intervention may yield a higher quality-of-life gain in less advanced disease states.
The results underscore the biologic's robust performance across different exacerbation risk profiles and reinforce the therapeutic relevance of IL-5 inhibition in COPD with eosinophilic inflammation. Notably, the consistency of benefit across endpoints, including exacerbation severity, healthcare utilisation, and symptom improvement, supports the use of Nucala as an add-on to triple therapy in appropriately selected patients.
From a commercial perspective, Nucala is well-positioned to expand its footprint in respiratory medicine beyond its approved indications in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA). While not yet approved for COPD, with a delay in the FDA's decision after a PDUFA date set for May 7, the totality of evidence across METREX, METREO, and MATINEE provides a strong foundation for regulatory engagement. In particular, the inclusion of a high-eosinophil population (≥ 300 cells/μL) aligns with emerging precision medicine strategies that favour biomarker-guided therapeutic decisions.
Nucala's performance in MATINEE strengthens its positioning as a mature and clinically validated option for eosinophilic phenotypes. With the recent approval of Sanofi and Regeneron's Dupixent for COPD with type 2 inflammation, the competitive landscape is becoming increasingly stratified by biomarker-driven segmentation. Key opinion leaders interviewed by GlobalData note that while Nucala targets a narrower IL-5-specific pathway, its established safety profile, multi-indication approval history, and payer familiarity may enable faster uptake if approved for COPD.
Moreover, Nucala's consistent effect regardless of baseline severity distinguishes it from competitors that primarily show benefit in higher-risk populations. This broader clinical utility, paired with a differentiated label strategy, could help GSK capture market share in the emerging eosinophilic COPD segment. However, future success will depend on securing regulatory approval, optimising companion diagnostic use, and positioning against Dupixent's more upstream mechanism of action. Market access stakeholders will also demand real-world cost-effectiveness data, particularly in light of the high treatment burden in COPD and constrained healthcare budgets globally.
Ultimately, the MATINEE results highlight Nucala's potential to become a foundational agent in eosinophilic COPD management, provided strategic alignment across regulatory, clinical, and access domains is achieved.
"ATS 2025: Nucala reduces COPD exacerbations, regardless of severe event history" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand.
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