Mitiperstat 5 mg daily fails to improve time to first exacerbation in COPDTrial shows mitiperstat does not reduce COPD flare-ups
The European respiratory journalPublished November 6, 2026Study authors: Saralaya Dinesh, Mustapa M Nubli, Ferreira João, Kocks Janwillem W H, Brailsford Wayne, Rosengren Sa…PubMed ↗NCT05492877 ↗DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Note that mitiperstat 5 mg daily did not improve time to exacerbation in patients with moderate-to-severe COPD.
This Phase 2a randomized controlled trial enrolled 381 adults aged 40 to 80 years with moderate-to-severe COPD who were at high risk of exacerbation and receiving dual or triple inhaled therapy. Participants were randomized to receive either mitiperstat 5 mg once daily for up to 24 weeks or a placebo.
The primary outcome was the time to first composite end-point for exacerbations in COPD (COPDCompEx) event. Results showed no improvement with mitiperstat, reporting a hazard ratio (HR) of 1.07 (90% CI 0.87-1.32; p=0.599). Specifically, 125 (66.1%) mitiperstat-treated patients and 125 (65.1%) placebo-treated patients reached the endpoint.
Secondary outcomes, including time to first moderate-to-severe COPD exacerbation, post-BD FEV, respiratory symptoms, and disease impact, also showed no improvement. For the time to first moderate-to-severe COPD exacerbation, the HR was 1.23 (90% CI 0.88-1.73). Regarding safety, 7 mitiperstat-treated participants and 2 placebo-treated participants developed pneumonia. Due to the lack of efficacy and the risk of pneumonia, the benefits of mitiperstat are not supported for COPD treatment.
How this fits prior evidence
How this fits prior evidence: This finding addresses a gap in pharmacological management for COPD. While prior coverage has highlighted the role of high-intensity interval training, complementary therapies, and the limitations of digital medicine in COPD, this trial specifically evaluates the efficacy of mitiperstat. The results indicate that mitiperstat does not provide a measurable benefit over placebo for exacerbation reduction in this population.
Researchers conducted a Phase 2a trial to see if the drug mitiperstat could help people with moderate-to-severe chronic obstructive pulmonary disease (COPD). The study included 381 adults who were at high risk for flare-ups and were already using standard inhaled therapies. Participants took either 5 mg of mitiperstat daily or a placebo for up to 24 weeks.
The results showed that mitiperstat did not improve the time until a patient experienced a flare-up compared to the placebo. Additionally, the drug did not improve lung function, reduce respiratory symptoms, or lessen the overall impact of the disease.
Safety data showed that some participants in both the treatment and placebo groups developed pneumonia. Because the drug did not provide any measurable benefits for symptoms or flare-ups, the study suggests that the risks may outweigh the benefits of using mitiperstat for COPD. Patients should continue to work with their doctors to manage their current treatment plans.
What this means for you:
The drug mitiperstat did not show any benefit in preventing COPD flare-ups or improving lung symptoms.
Common questions
Does mitiperstat help prevent COPD flare-ups?
No, the study found no improvement in the time to the first flare-up for patients taking mitiperstat compared to those taking a placebo. The results were similar for both groups, meaning the drug did not provide a measurable benefit in preventing these events.
Did mitiperstat improve lung function or symptoms?
The study found no improvement in lung function (post-BD FEV) or in respiratory symptoms for those taking mitiperstat. It also did not show a positive impact on the overall burden of the disease for patients with moderate-to-severe COPD.
Is mitiperstat safe for people with COPD?
The study reported that 7 people taking mitiperstat and 2 people taking a placebo developed pneumonia. Because the drug did not show any benefit for symptoms or flare-ups, the study suggests the risks may outweigh the benefits. Talk to your doctor about your specific treatment.
BACKGROUND: Neutrophilic inflammation is a common feature of COPD. Mitiperstat, an inhibitor of myeloperoxidase expressed in neutrophils, may have potential as a COPD treatment.
METHODS: This phase 2a, randomised, placebo-controlled, double-blind, parallel-arm, event-driven trial evaluated the efficacy and safety of mitiperstat 5 mg once daily for up to 24 weeks (CRESCENDO; ClinicalTrials.gov: NCT05492877). Adults (40-80 years) with moderate-to-severe COPD, at high risk of exacerbation and receiving dual or triple inhaled therapy were included. The primary end-point was time to first composite end-point for exacerbations in COPD (COPDCompEx) event. Secondary end-points included time to first moderate-to-severe COPD exacerbation, post-bronchodilator forced expiratory volume in 1 s (post-BD FEV) change at week 12, respiratory symptoms, disease impact and safety.
RESULTS: Overall, 381 participants (mean age 66.0 years; 39.6% female) were randomised to mitiperstat (n=189) or placebo (n=192). In total, 125 (66.1%) mitiperstat-treated 125 (65.1%) placebo-treated participants experienced COPDCompEx events over 24 weeks. There was no improvement in time to first COPDCompEx event (hazard ratio (HR) 1.07, 90% CI 0.87-1.32; p=0.599) or time to first moderate-to-severe COPD exacerbation (HR 1.23, 90% CI 0.88-1.73) with mitiperstat placebo. Improvements in post-BD FEV, respiratory symptoms or disease impact were not seen with mitiperstat. A similar proportion of participants in both groups reported adverse events; seven mitiperstat-treated participants and two placebo-treated participants had pneumonia during the study.
CONCLUSION: These results indicate that the risks outweigh the benefits of mitiperstat as a treatment for COPD.
