Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial

This phase 2 study (n=535) suggests p38 MAPK inhibition with oral losmapimod was well tolerated in NSTEMI patients and might improve outcomes after ACS. Note: The study lasted 12 weeks and investigated effect of losmapimod on inflammatory markers (not patient related outcomes).

Losmapimod is an orally active inhibitor of p38 mitogen-activated protein (MAP) kinase under investigation for acute coronary syndromes (ACS). It is being developed by GSK who also funded this study. Phase 3 trials for losmapimod are underway.

 

Efficacy outcomes considered in this study were: levels of high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) at 72 hours and 12 weeks, and troponin I area under the curve (AUC) over 72 hours. The losmapimod groups were pooled for analysis. A total of 526 patients received at least one dose of the study treatment. The results for the efficacy outcomes showed:

 

 

·         HsCRP concentrations at 72 h were lower in the losmapimod group than in the placebo group (geometric mean 64.1 nmol/L, 95% CI 53.0—77.6 vs 110.8 nmol/L, 83.1-147.7; p=0.0009) but were similar at 12 weeks.

·         Early geometric mean BNP concentrations were similar at 72 h but significantly lower in the losmapimod group at 12 weeks (37.2 ng/L, 95% CI 32.3-42.9 vs 49.4 ng/L, 38.7-63.0; p=0.04).

·         Mean troponin I AUC values did not differ.

Safety outcomes showed no difference between groups.