Mepolizumab reduces exacerbations in COPD with type 2 inflammation

Key takeaways:

• Patients receiving mepolizumab vs. placebo had a smaller number of moderate/severe exacerbations at weeks 52 and 104.
• Mepolizumab prolonged the time to first moderate/severe exacerbation.

With mepolizumab vs. placebo, patients with COPD and type 2 inflammation experienced significantly fewer moderate/severe exacerbations in a year, according to results published in The New England Journal of Medicine.

Ian D. Pavord

“Increased awareness of the presence of type 2 inflammation in patients with COPD and the potential beneficial effect of mepolizumab” are the main impacts of this study, Ian D. Pavord, MA, DM, FRCP, FERS, FMedSci, professor of respiratory medicine at the University of Oxford and honorary consultant physician at the Oxford University Hospitals, told Healio.

In the multicenter, double-blind, randomized, placebo-controlled phase 3 MATINEE trial, Sciurba and colleagues evaluated 804 patients with COPD and type 2 inflammation (blood eosinophil count ≥ 300 cells/μL) receiving inhaled triple therapy to determine the impact of subcutaneous 100 mg mepolizumab (Nucala, GSK) vs. placebo every 4 weeks on moderate/severe exacerbations at 52 to 104 weeks.

Researchers also analyzed drug safety and scores on the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS-COPD) at week 52 of treatment vs. baseline in the two groups.

As Healio previously reported, the FDA accepted to review a supplemental new drug application for mepolizumab — including data from the MATINEE trial — for treating patients with COPD plus an eosinophilic phenotype in December 2024. According to a GSK press release, the FDA assigned a Prescription Drug User Fee Act target date of May 7.

Within the study population, 403 patients (mean age, 66.4 years; 32% women; geometric mean blood eosinophil count, 480 cells/μL) received mepolizumab, and 401 patients (mean age, 66 years; 31% women; geometric mean blood eosinophil count, 480 cells/μL) received placebo.

Notably, some patients received their treatment for a fixed duration of 52 weeks (mepolizumab, n = 170; placebo, n = 175), whereas others received their treatment for a variable duration with a maximum of 104 weeks (mepolizumab, n = 233; placebo, n = 226), according to the study.

Results

At the 52-week mark, patients receiving mepolizumab vs. placebo had a significant decrease in the annualized rate of moderate or severe exacerbations by 21% (rate ratio [RR] = 0.79; 95% CI, 0.66-0.94), with 0.8 events per year vs. 1.01 events per year. Researchers found a similar pattern at week 104, with a lower cumulative number of moderate or severe exacerbation among those receiving mepolizumab.

In addition to lowering the annualized exacerbation rate, mepolizumab prolonged the time to first moderate or severe exacerbation. Researchers reported that 419 days passed before the first moderate or severe exacerbation in the mepolizumab group, whereas only 321 days passed before this occurrence in the placebo group (HR through week 104 = 0.77; 95% CI, 0.64-0.93).

For the three health-related quality of life and symptom measures, the study reported that those receiving mepolizumab and those receiving placebo had similar proportions of patients who achieved “response,” which differed based on the evaluated measure.

CAT responders had a two-point reduction or higher between baseline and week 52 (mepolizumab, 41% vs. placebo, 46%), E-RS-COPD responders had a two-point reduction or higher between week 49 and week 52 (31% vs. 34%) and SGRQ responders had a four-point reduction or higher between baseline and week 52 (50% vs. 46%), according to the study.

Based on least-squares mean changes, researchers observed greater improvements with mepolizumab vs. placebo in the SGRQ (least-squares mean difference, –2.3; 95% CI, –4.6 to 0.1) and the E-RS-COPD (least-squares mean difference, –0.2; 95% CI, –1 to 0.6) during exploratory analysis.

Researchers also examined exacerbations leading to an ED visit and/or hospitalization in each group and found a lower annualized rate among patients who received mepolizumab vs. placebo (0.13 vs. 0.2 events per year; RR = 0.65; 95% CI, 0.43-0.96).

In exploratory analysis, patients receiving mepolizumab vs. placebo had a smaller number of severe exacerbation events per year (0.1 vs. 0.15; RR = 0.66; 95% CI, 0.43-1.01).

In terms of lung function, those receiving placebo had more improvement in prebronchodilator FEV₁ at the 52-week mark than those receiving mepolizumab (least-squares mean change, 33.6 mL vs. 24.6 mL), according to the study.

Treatment safety

Researchers found that both groups had comparable proportions of patients that experienced adverse events (mepolizumab, 74% vs. placebo, 77%), serious adverse events (25% vs. 28%) and death (3% in both groups).

According to the study, frequent adverse events included exacerbation/worsening of COPD (mepolizumab, 12%; placebo, 15%) and severe acute respiratory syndrome coronavirus 2 infection (12% in both groups). Exacerbation/worsening of COPD was also the most frequent serious adverse events (mepolizumab, 11%; placebo, 14%), followed by pneumonia (3% in both groups).

For several cardiovascular outcomes (death from a cardiovascular cause, nonfatal myocardial infarction, nonfatal stroke, fatal/nonfatal myocardial infarction and fatal/nonfatal stroke), each occurred in 1% or less of patients receiving mepolizumab and patients receiving placebo.

With the FDA’s target action date for the drug less than a week away, Pavord told Healio the findings from this trial provide “clear evidence of efficacy against a clinically important outcome in a population who have high levels of morbidity and few other treatment options.”

Looking ahead, future studies may investigate earlier intervention, Pavord said.

“There is interest in earlier intervention in patients with active type-2 inflammation (ie, high disease activity) to prevent disease progression,” Pavord told Healio. “The problem with this and other studies in COPD is that this progression has already occurred.”

Reference:

For more information:

Ian D. Pavord, MA, DM, FRCP, FERS, FMedSci, can be reached at ian.pavord@ndm.ox.ac.uk.