Eli Lilly and Company: Xigris Sustains Survival Long Term in Severe Sepsis Patients; Studies Show Drug Saves Lives Without Lengthening Hospital Stays.

Business Editors and Health/Medical writers

INDIANAPOLIS--(BUSINESS WIRE)--Nov. 5, 2002

Xigris(R) (drotrecogin alfa (activated)) sustains survival of severe sepsis patients long term, according to study results presented at the 68th annual International Scientific Assembly of the American College of Chest Physicians (ACCP) in San Diego. In one of four abstracts on Xigris presented today, the analysis indicates that the drug also saves lives without lengthening hospital stays compared with the use of standard care alone.

Xigris already had proved effective in decreasing the short-term risk of death (28 days) in adults with life-threatening severe sepsis in the landmark PROWESS Phase III clinical trial. Eli Lilly and Company (NYSE: LLY) received FDA approval for Xigris in November 2001 to reduce mortality in adult severe sepsis patients at high risk of death (e.g., as determined by APACHE II(1)) and was recently approved by the European Commission for use in the 15 countries it represents.

Xigris Sustains Survival

Results of a long-term follow-up analysis of PROWESS (n=1,690), conducted from September 2001 until April 2002, showed that reduction in mortality in Xigris-treated patients was sustained over the duration of the study, which followed patients up through two and a half years.(2) "Xigris has already proven that it dramatically improves patients' chances of making it through the most dangerous stage of life-threatening severe sepsis - those first 28 days," said study researcher Derek C. Angus, M.D., M.P.H., associate professor of anesthesiology and critical care medicine, University of Pittsburgh. "Our new data show that the survival benefit of Xigris is sustained over the long term. These findings are wonderful news - and offer much-needed hope - for thousands of patients with severe sepsis and their families."

No Increase in Hospital Time

In the PROWESS trial, treatment with Xigris plus standard therapy in adults with severe sepsis significantly reduced 28-day all-cause mortality compared with placebo plus standard therapy. The long-term follow-up analysis showed Xigris significantly decreased in-hospital mortality (absolute reduction of 5.2 percent) without incurring extra time in the hospital. Among hospital survivors with known discharge status, patient discharge locations - nursing home, ICU, other hospital location - were similar between arms, with about 75 percent of the excess survivors being discharged directly to home.(3)

"These data indicate that treatment with Xigris is an investment that pays off," said William Macias, M.D., Ph.D., medical director, Xigris product team, Eli Lilly and Company. "Xigris saves lives and does so without requiring any excess hospital stay, allowing the majority of survivors to go home rather than requiring care at another institution."

New Data Reaffirms Efficacy and Safety Profile of Xigris

Additional data presented today demonstrate that the survival rate in Xigris-treated patients from all clinical trials to date has remained consistent with the PROWESS clinical trial results.

In five clinical trials and two compassionate use studies of Xigris, the 28-day mortality rate for all patients receiving active treatment was 25.3 percent, comparable to the 24.7 percent Xigris mortality and less than the 30.8 percent placebo mortality demonstrated in the PROWESS trial. A comprehensive review of cumulative safety data from both clinical trials and postapproval experience in the United States shows that the only significant adverse event associated with Xigris is bleeding, and the data suggest risk of bleeding is generally manageable. Importantly, this analysis indicates that such events were frequently associated with other hemorrhage-causing factors, such as invasive procedures and thrombocytopenia (platelets less than 30,000 per milliliter).(4)

About Xigris

Xigris (drotrecogin alfa (activated)) is a recombinant form of human Activated Protein C. It is administered by intravenous infusion and is available in 5 and 20 mg vials.

In November 2001, the U.S. Food and Drug Administration approved Xigris for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death (e.g., as determined by APACHE II). The relative risk of death for patients receiving Xigris and who were at high risk of death (as defined by an APACHE II score of greater than or equal to 25) was reduced by 29 percent in the PROWESS trial involving 1,690 patients (p=0.0002).

Efficacy of Xigris has not been established in adult patients with severe sepsis and a lower risk of death. Safety and efficacy have not been established in pediatric patients with severe sepsis. Lilly is undertaking large-scale trials to investigate the use of Xigris in lower risk patients and in children with severe sepsis, as well as the optimal use of low-dose heparin with Xigris.

Bleeding events are common in patients with severe sepsis. In the PROWESS trial, bleeding was the most common adverse reaction associated with Xigris therapy. Serious bleeding events, including intracranial hemorrhage, were observed during the 28-day study period in 3.5 percent of Xigris-treated patients and 2.0 percent of placebo-treated patients. The difference in serious bleeding occurred primarily during infusion.

For complete Xigris (drotrecogin alfa (activated)) prescribing information and labeling, call 800-423-2313 or visit www.Xigris.com.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at www.lilly.com.

(1) Acute Physiology and Chronic Health Evaluation Score

(2) Angus D, et al. The Effects of Drotrecogin Alfa (Activated) on

Long-Term Survival After Sepsis. CHEST, Oct. 2002, Vol. 122,

No. 4 (suppl), p.51S.

(3) Laterre PF, et al. The Effects of Drotrecogin Alfa (Activated)

on Hospital Mortality, Length of Stay, and Discharge Location.

CHEST, Oct. 2002, Vol. 122, No. 4 (suppl), p.51S.

(4) Bernard G., et al. Drotrecogin Alfa (Activated) Safety Update.

CHEST, Oct. 2002, Vol. 122, No. 4 (suppl), p.50S.