MITIPERSTAT did not improve exacerbation outcomes, lung function or respiratory symptoms in people with chronic obstructive pulmonary disease (COPD), according to the phase 2a CRESCENDO trial.
The randomised study tested the oral myeloperoxidase inhibitor against placebo as an addition to existing inhaled treatment. Pneumonia occurred more frequently in the mitiperstat group, contributing to the researchers’ conclusion that its risks outweighed its benefits in this setting.
The trial investigated whether inhibiting myeloperoxidase, an enzyme associated with neutrophils, could offer an additional treatment approach for patients whose COPD remained problematic despite standard therapy.
Adults aged 40–80 years with moderate-to-severe COPD and an increased risk of exacerbations were eligible. Participants continued established dual or triple inhaled therapy while receiving mitiperstat 5 mg or placebo once daily for up to 24 weeks.
The protocol defined increased risk through factors including previous exacerbations, frequent productive cough or substantially reduced lung function. This allowed recruitment beyond patients selected solely on their recent exacerbation history.
The study used a partially decentralised design, combining remote and in-person assessments with home monitoring. Patient input informed the design and participant materials, with the aim of reducing the burden of trial participation.
Overall, 381 participants were randomised: 189 to mitiperstat and 192 to placebo. The primary outcome was time to a first COPDCompEx event, a composite incorporating clinical exacerbations and deterioration detected through symptom, reliever-use and peak-flow monitoring.
Such events occurred in 66.1% of the mitiperstat group and 65.1% of the placebo group. There was no significant improvement in time to the first event (hazard ratio: 1.07; 90% confidence interval: 0.87–1.32).
Mitiperstat also failed to improve time to a first moderate-to-severe exacerbation. Secondary assessments found no benefit in lung function, respiratory symptoms or disease impact.
Although overall adverse event reporting was similar between groups, pneumonia occurred in seven mitiperstat-treated participants and two receiving placebo. These small numbers require careful interpretation, but the imbalance adds concern when considered alongside the absence of efficacy.
The trial’s results do not support adding this mitiperstat regimen to inhaled treatment for the population studied. They also illustrate why a plausible inflammatory target must demonstrate both clinical benefit and acceptable safety in controlled trials.
The findings relate to this drug, dose and study setting; they do not establish that all approaches targeting neutrophilic inflammation will be ineffective in COPD.
Reference
Saralaya D et al. A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with COPD. Eur Respir J. 2026;68(5):2502567. doi:10.1183/13993003.02567-2025.
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