A post-hoc subgroup analysis of data from a six month clinical trial comparing the efficacy and safety of losmapimod in moderate-severe COPD patients with ≤2% and >2% blood eosinophils

Respir Med. 2015 Jul;109(7):860-9. doi: 10.1016/j.rmed.2015.05.003. Epub 2015 May 20.


Background: A six month study of the p38 MAPK inhibitor, losmapimod, suggested a trend in reducing COPD exacerbations with the 15 mg twice daily dose.

Objective and methods: Using data from this study which evaluated the efficacy of twice daily losmapimod, 2.5 mg, 7.5 mg, and 15 mg, versus placebo in patients with moderate-to-severe COPD, we analysed the effect of losmapimod in reducing the rate of moderate/severe exacerbations in patient subgroups with ≤2% and >2% blood eosinophils at baseline. Lung function, fibrinogen and hsCRP were also evaluated.

Results: In the ≤2% eosinophil subgroup, there was an exposure-related reduction in the rate of moderate/severe exacerbations with losmapimod relative to placebo (losmapimod 15 mg: 55% reduction; losmapimod 7.5 mg: 29%; losmapimod 2.5 mg: 10%); with the 15 mg dose reaching statistical significance (15 mg/placebo mean rate ratio [95% CI]: 0.45 [0.22; 0.90]). There was also an improvement in lung function with 15 mg losmapimod over Weeks 1-12. No improvement in the rate of moderate/severe exacerbations or post-bronchodilator FEV1 was observed for subjects treated with Losmapimod compared to placebo in the patient subgroup with blood eosinophils >2% at baseline. Transient reductions in fibrinogen and hsCRP were observed with losmapimod 7.5 mg and 15 mg in both eosinophil subgroups.

Conclusions: These findings indicate eosinophil-related heterogeneity within COPD and suggest that losmapimod could be a potential therapy to reduce exacerbations in COPD patients with eosinophil levels ≤2%. This needs to be explored further in a prospectively designed study with pre-specified criteria for blood eosinophil subgroups in COPD patients.

Keywords: COPD; Eosinophils; Exacerbations; Losmapimod; p38 MAPK inhibitor.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cyclopropanes / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Eosinophils / pathology*
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pyridines / administration & dosage*
  • Severity of Illness Index
  • Treatment Outcome
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors


  • 6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide
  • Cyclopropanes
  • Pyridines
  • p38 Mitogen-Activated Protein Kinases