Phase III results using E 5564 (Eisai) show no significant benefit for Sepsis

A Phase III trial to evaluate the safety and efficacy of E 5564 (eritoran), from Eisai, in reducing mortality in patients with severe Sepsis shows the drug failed to demonstrate a significant effect on reducing all-cause 28-day mortality or 1-year mortality, compared with placebo. The randomized, multinational trial was conducted in 197 intensive care units. Patients were enrolled from June 2006 to September 2010 and final follow-up was completed in September 2011. Patients with severe sepsis were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium or placebo. The primary end point for the study was 28-day all-cause mortality. The secondary end points were all-cause mortality at 3, 6, and 12 months.

Results show that treatment with eritoran did not offer significant reductions in the primary study end point of 28-day mortality in the modified intent-to-treat analysis (randomized patients who received at least 1 dose) population; 28.1 percent in the eritoran group vs. 26.9 percent in the placebo group. There was also no significant difference in the secondary end point of 1-year all-cause mortality: 44.1 percent in the eritoran group vs. 43.3 percent in the placebo group. Eritoran was well tolerated with comparable numbers of treatment-emergent adverse events (TEAEs) between eritoran and placebo groups. Results wre published in JAMA. See: "Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe SepsisThe ACCESS Randomized Trial." Steven M. Opal et al. JAMA. 2013;309(11):1154-1162. doi:10.1001/jama.2013.2194