Eisai Announce Phase II Results, Plans to Initiate Phase III Clinical Trial Program for Eritoran as a Treatment for Severe Sepsis


Applied Clinical Trials

Eisai's decision is based on Phase II study results that showed a reduction in mortality in eritoran-treated patients versus placebo.

RIDGEFIELD PARK, NJ – August 29, 2005 – Eisai Co., Ltd. (Headquarters: Tokyo, President: Haruo Naito) and Eisai Medical Research Inc. (Ridgefield Park, Mindell Seidlin, MD, President) announce today that they plan to initiate a Phase III clinical program for eritoran (E5564) as a potential treatment for severe sepsis. Eisai's decision is based on Phase II study results that showed a reduction in mortality in eritoran-treated patients versus placebo. Eisai plans to initiate a Phase III clinical program after consulting with regulatory authorities in the United States, Canada and European Union.

The study, conducted in North America, involved 293 patients randomized to three groups, eritoran high dose (105mg/6days), eritoran low dose (45mg/6days) and placebo. Eritoran was administered twice daily by intravenous infusion. The goal of the study was to test whether eritoran could reduce the 28-day all-cause mortality by at least 5% compared to placebo. The study was not sized to detect a statistically significant difference in mortality. The mortality in the high-dose group was reduced by 6.4% (p=0.34) compared to placebo. Mortality was 33.3% in placebo, 32.0% in the low-dose group and 26.9% in the high-dose group.

About 80% of the patients were compliant with the protocol. The mortality rate in these patients was reduced by 12.2% (p=0.09&sup1) in the high-dose group compared to placebo. Mortality was 34.6% in placebo, 32.5% in the low-dose group and 22.4% in the high-dose group.

The greatest benefit occurred in the population at the highest risk of mortality as assessed by a standard assessment tool that predicts mortality. In patients who were considered at higher risk of death, mortality among placebo patients was 50.9%, 37.9% in low-dose patients and 33.3% in high-dose patients. The reduction of mortality in low- and high-dose patients compared to placebo was 13.0% (p=0.171) and 17.6% (p=0.071), respectively.The drug appeared to be well tolerated. Phlebitis, or inflammation of the vein, was observed in 6.7% of patients dosed with eritoran through a peripheral vein. It showed a tendency to recover with time.

Sepsis is a condition involving infection and inflammation. The body's normal response is to set off a limited chain reaction to fight the infection. In severe sepsis, this systemic response escalates into an overreaction by the body that leads to organ failure and may become life-threatening.

Toll-like receptor 4 (TLR4) is linked to the innate immune system and is thought to play an important role in the course of severe sepsis. It can be activated by endotoxin, which is associated with the outer membranes of certain gram-negative bacteria, and can then trigger the inflammatory cascade, or chain reaction.

Discovered by scientists at the Eisai Research Institute of Boston, Inc., eritoran is believed to block endotoxin's activation of TLR4. In a Phase I study conducted in the United States, eritoran blocked signs and symptoms (such as fever and rapid heart rate) and the production of inflammatory cytokines induced by endotoxin infusion in healthy volunteers.

Eisai's research and development efforts regarding eritoran and severe sepsis exemplify the company's human health care mission, which is to satisfy unmet medical needs and increase benefits to patients and their families. More than 750,000 people in the United States alone develop severe sepsis each year. The mortality rate for severe sepsis is 28%-50%.

About Eisai Co., Ltd.

Eisai Co., Ltd. is a research-based human health care company that discovers, develops and markets products in more than 30 countries. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide health care system. Eisai employs more than 7,700 people worldwide.

About Eisai Medical Research Inc.

Eisai Medical Research Inc. is a U.S. pharmaceutical subsidiary of Eisai Co., Ltd. Eisai Medical Research Inc. was established to focus solely on clinical research and to expedite clinical drug development of new chemical entities and of new indications for marketed products.

&sup1 p values are of exploratory nature only; no multiplicity adjustment was made.

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