Nucala (mepolizumab) approved by US FDA for use in adults with chronic obstructive pulmonary disease – GSK

GSK plc announced that the FDA has approved Nucala (mepolizumab) as an add-on maintenance treatment for adult patients with inadequately controlled COPD and an eosinophilic phenotype. FDA’s approval was based on data from the positive MATINEE and METREX phase III trials. Across these trials, mepolizumab showed a clinically meaningful and statistically significant reduction in the annualised rate of moderate/severe exacerbations versus placebo in a wide spectrum of COPD patients with an eosinophilic phenotype. Preventing exacerbations is a key goal of COPD management. Exacerbations are devastating for patients, known to cause irreversible lung damage, worsening of symptoms and increased mortality. The incidence of adverse events was similar between placebo and mepolizumab groups.

Both MATINEE and METREX are phase III, randomised (1:1), double-blind, parallel-group trials assessing the efficacy and safety of mepolizumab 100 mg as add-on therapy, administered subcutaneously every 4 weeks versus placebo in addition to optimal inhaled triple therapy (dual long-acting bronchodilators plus inhaled corticosteroid). MATINEE assessed the efficacy and safety of mepolizumab for 52–104 weeks, in 804 patients with COPD with evidence of type 2 inflammation, characterised by a blood eosinophil count (≥300 cells/µL). Patients could participate with a range of clinical presentations of COPD including chronic bronchitis, emphysema only or a combination of both. The condition of patients ranged in severity from moderate to very severe, or stages 2-4 as assessed by the medically recognised scale of Global Initiative for Chronic Obstructive Lung Disease (GOLD). The full analysis of MATINEE included 403 patients enrolled on the mepolizumab arm and 401 on placebo, all of whom had experienced exacerbations in the previous year despite receiving optimised inhaled maintenance therapy.

The full study results from MATINEE were recently published in the New England Journal of Medicine with further data presented at the 2025 American Thoracic Society International Congress, including additional sub-analyses in patients with or without cardiovascular comorbidities, varying severities of prior exacerbations, and those with chronic bronchitis, emphysema-only or both.

In METREX, the efficacy and safety of mepolizumab was evaluated for 52 weeks in 836 patients randomised (1:1) to mepolizumab or placebo across two groups, the eosinophilic phenotype group (blood eosinophil count of ≥150 cells/µl at study entry or ≥ 300 cells/µl within the past year) or the non-eosinophilic phenotype group (blood eosinophil count of <150 cells/µl at study entry and no evidence of ≥300 cells/µl within the past year). The study results from METREX were published in 2017 in the New England Journal of Medicine.

In both MATINEE and METREX trials, mepolizumab demonstrated a statistically significant reduction in the annualised rate of moderate or severe exacerbations compared with placebo, in patients with an eosinophilic phenotype, when added to triple inhaled therapy (MATINEE: rate ratio [RR], 0.79; 95% confidence interval [CI], 0.66 to 0.94; P=0.01) (METREX: rate ratio, 0.82; 95% CI, 0.68 to 0.98; adjusted P=0.04). In a pre-defined secondary endpoint in MATINEE, the annualised rate of COPD exacerbations requiring ED visits and/or hospitalisation was reduced in the mepolizumab group when compared with placebo (rate ratio [RR] of 0.65; 95% CI: 0.43, 0.96 [not statistically significant due to a failure of an endpoint higher in the pre-defined statistical testing hierarchy]).

Mepolizumab is currently not approved for use in COPD in any other country. Regulatory submissions are under review in China and Europe.

Dr. Jean Wright, Chief Executive Officer of the COPD Foundation said: “COPD isn’t just a disease, it’s a relentless cycle. For individuals living with COPD, managing exacerbations is an ongoing challenge, even with inhaled maintenance therapy. Biologics like mepolizumab are providing renewed optimism for those affected by COPD.”

Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK, said: “The approval of Nucala in the US provides an important option for COPD patients. Long-term follow-up studies have demonstrated that exacerbations are the single most important predictor of future risk, with particularly poor outcomes in those requiring hospital visits or admissions. There is hope for improved care for COPD patients with an eosinophilic phenotype, including those with a BEC threshold as low as ≥150cells/μL who need new options like Nucala to support their treatment journey.”

See citations- Pavord ID, Chanez P et al. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med 2017, 377:1613 DOI: 10.1056/NEJMoa1708208.

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.