FDA Approves Mepolizumab for Eosinophilic COPD

As of today, May 22, the FDA has approved mepolizumab (Nucala) as an add-on maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype.1 The news comes 2 weeks after the FDA missed the therapy's original Prescription Drug User Fee Act date of May 7.

“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," Jean Wright, MD, MBA, Chief Executive Officer of the COPD Foundation, said in a statement.1

GSK’s biologics license application (BLA) was supported by data from the phase 3 MATINEE trial, which the company reported full data from earlier this month.2 The FDA previously accepted the BLA in December 2024 after initially rejecting GSK’s first proposal in 2018.3

MATINEE was a double-blind, randomized, placebo-controlled trial that enrolled 804 patients with COPD, a history of exacerbations, and a blood eosinophil count of at least 300 cells per microliter who were receiving triple inhaled therapy. The trial’s population included those with chronic bronchitis, emphysema only or both. The participants were randomized 1:1 to receive mepolizumab 100 mg (n = 403) or placebo (n = 401) subcutaneously every 4 weeks for 52 to 104 weeks.

The investigators found that mepolizumab demonstrated a statistically significant and clinically meaningful 21% reduction in the annualized rate of moderate or severe exacerbations (0.80 events per year) compared to placebo (1.01 events per year; rate ratio, 0.79; 95% CI, 0.66 to 0.94; P = .01), successfully meeting the primary endpoint. Time to first moderate or severe exacerbation was also significantly prolonged with mepolizumab, with a median of 419 days compared to 321 days with placebo (hazard ratio, 0.77; 95% CI, 0.64 to 0.93; P = .009).4

Patients also had a nominally significant reduction in exacerbations leading to emergency department visits and/or hospitalization. However, no significant between-group differences were observed in health-related quality of life or symptom measures, and further secondary endpoints were not formally tested. Additionally, patients with clinician-assessed chronic bronchitis had a 31% reduction in annualized exacerbation rates with mepolizumab (rate ratio, 0.69; 95% CI, 0.51 to 0.93; n = 338.

“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. Today 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," Kaivan Khavandi, SVP, Global Head, Respiratory, Immunology & Inflammation R&D, GSK, added.1

“It seems that mepolizumab very likely has a place in the treatment of a subset of patients with COPD who are at risk for exacerbations. However, there is work to do to better define the target population, so let’s try, try, and try again,” Mark T. Dransfield, MD, and Daiana Stolz, MD, from University of Alabama at Birmingham, Alabama, and University of Freiburg, Germany, respectively, wrote in a recent editorial about mepolizumab’s data for COPD.5

REFERENCES

1. Nucala (mepolizumab) approved by US FDA for use in adults with chronic obstructive pulmonary disease (COPD). News release. GSK. May 22, 2025. https://www.gsk.com/en-gb/media/press-releases/nucala-mepolizumab-approved-by-us-fda/
2. US FDA accepts GSK’s submission for the use of Nucala (mepolizumab) in COPD. December 9, 2024. https://us.gsk.com/en-us/media/press-releases/us-fda-accepts-gsk-s-submission-for-the-use-of-nucala-mepolizumab-in-copd/
3. GSK receives complete response letter from US FDA for use of mepolizumab in COPD patients. News release. GSK. September 7, 2018. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-complete-response-letter-from-us-fda-for-use-of-mepolizumab-in-copd-patients/
4. Sciruba FC, Criner GJ, Christenson SA, et al. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype. N Engl J Med. 2025;392:1710-1720. DOI: 10.1056/NEJMoa2413181
5. Dransfield MT and Stolz D. Mepolizumab in COPD — If at First You Don’t Succeed. N Engl J Med 2025;392:1746-1748. DOI: 10.1056/NEJMe2503292