Nucala Reduces COPD

The trial evaluated mepolizumab, a monoclonal antibody targeting interleukin-5 (IL-5), in a wide spectrum of patients with COPD, including the most severe and difficult to treat as categorised in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Patients recruited had evidence of type 2 inflammation, characterised by blood eosinophil count and included those with chronic bronchitis, emphysema-only or both. The monthly administration of mepolizumab demonstrated improvement across all exacerbation endpoints, which were maintained over the 2-year (up to 104 weeks) study period.

MATINEE is a phase III, randomised (1:1), double-blind, parallel-group trial assessing the efficacy and safety of mepolizumab 100 mg as add-on therapy, administered subcutaneously every 4 weeks for 52–104 weeks, versus placebo in addition to optimal inhaled triple therapy (dual long-acting bronchodilators plus inhaled corticosteroid).

In the full population studied, mepolizumab showed a clinically meaningful and statistically significant 21% reduction in the annualised rate of moderate/severe exacerbations versus placebo, meeting the primary endpoint for MATINEE (rate ratio [95% confidence interval (CI)]: 0.79 [0.66, 0.94]; P=0.011) (AER mepolizumab = 0.80 exacerbations per year versus placebo = 1.01) n= 804; mepolizumab = 403, placebo = 401). In addition, mepolizumab also showed a 31% reduction in the annualised rate of moderate/severe exacerbations versus placebo in a post-hoc analysis of patients with clinician assessed chronic bronchitis only (rate ratio [95% CI]: 0.69 [0.51, 0.93] n=338: mepolizumab = 170, placebo = 168).

A 35% reduction in the annualised rate of exacerbations leading to emergency department visits and/or hospitalisation was shown with mepolizumab versus placebo, a secondary endpoint of the MATINEE study (rate ratio [95% CI]: 0.65 [0.43, 0.96] nominally significant after adjustment for multiplicity) (AER mepolizumab = 0.13 exacerbations per year versus placebo = 0.20)). Mepolizumab is the only biologic with data that shows a reduction in emergency department visits and/or hospitalisation in a phase III trial. Reducing hospitalisations is a key goal of COPD management. COPD-related hospitalisations are a major healthcare challenge and projected to become the number one cause of medical admissions. If hospitalised due to COPD, one in ten patients will die during the stay, up to one in four over the next year and half will lose their lives within five years.

High response rates were observed in Patient Reported Outcomes (PROs) in the mepolizumab group, however there was no difference observed for St George’s Respiratory Questionnaire (SGRQ), the COPD Assessment Test (CAT) and the Evaluating Respiratory Symptoms (E-RS) in the full study population versus placebo. The incidence of adverse events were similar between mepolizumab and placebo (mepolizumab vs placebo: 74% vs 77%), with the most frequent being exacerbation or worsening of COPD (mepolizumab vs placebo: 12% vs 15%) and COVID-19 infection (12% vs 12%).

Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK said: “The MATINEE results show that mepolizumab can help prevent exacerbations, including those leading to emergency department visits and/or hospitalisation. These exacerbations are devastating for patients, known to cause irreversible lung damage, worsening of symptoms and increased mortality. For decades, we have and will continue to push the boundaries of innovation to prevent disease progression and make a meaningful impact on the lives of people affected by COPD.”

 Frank Sciurba, Professor of Pulmonary, Allergy and Critical Care Medicine, and lead author of the MATINEE trial said: “Every physician will know the feeling of seeing a patient hospitalised due to an exacerbation that could have possibly been prevented. The MATINEE trial uncovers new possibilities in the treatment landscape for COPD patients with type 2 inflammation, as we strive to target drivers of disease and improve the lives of patients suffering with COPD.

See citation- Sciurba FC, Criner GJ, Christenson SA et al. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med . 2025, 392:1710 doi: 10.1056/NEJMoa2413181.