Drug aiming to reduce inflammation does not improve CV endpoints
The Losmapimod To Inhibit P38 MAP Kinase As A Therapeutic Target And Modify Outcomes After An Acute Coronary Syndrome (LATITUDE-TIMI 60) Trial: Primary Results Of Part AMichelle O’Donoghue (Brigham and Women's Hospital, Boston, MA, USA)
Presented at ACC 2016
Backgroundp38 mitogen-activated protein kinase (MAPK)-stimulated inflammatory processes have been suggested to contribute to atherogenesis, plaque destabilization and maladaptive processes in infarction and wound healing. Pilot data in a phase II trial supported the concept that the p38 MAPK inhibitor losmapimod may attenuate inflammation in the myocardium and vascular wall and thereby improve outcomes for patients after a myocardial infarction (MI).
The LATITUDE-TIMI 60 trial was a randomized, double-blind staged phase 3 trial to evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute MI. The initial phase of the study study included 3,500 patients at 322 hospitals in 34 countries. Half of the patients received 7.5 milligrams of losmapimod twice daily and half received a placebo. Part A consisted of a leading cohort (n=3,500) to provide an initial assessment of safety and exploratory efficacy before considering progression to Part B (n~22,000). The primary endpoint was CV death, MI, or urgent coronary revascularization. Selected secondary endpoints included CV death or MI and CV death or heart failure.
- Losmapimod reduced inflammation measured with hsCRP at 4 weeks (ratio of the mean for losmapimod compared with placebo, 0.76; 95% CI 0.62-0.91, P=0.004)) and 12 weeks (ratio of means 0.73, 95% CI 0.61-0.87, P<0.001)
- At 12 weeks, the primary endpoint was reached in 8.1% of losmapimod patients vs. 7.0% placebo (HR 1.16, 95% CI 0.91-1.47; P=0.24)
- The incidence of any on-treatment serious adverse event was 16.0% for patients on losmapimod and 14.2% for placebo
ConclusionAmong patients with acute MI, use of losmapimod did not reduce the risk of major ischemic CV events, compared with placebo. Because of these results, the second phase trial involving 22,000 patients will not go forward.
SourcePress release ACC 2016
This study was published simultaneously in JAMA