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Back To Vidyya Promising New Sepsis Drug Performs Well In Phase III Clinical Trials

Zovant Shows 19.4% Reduction In Sepsis Deaths

Eli Lilly and Company announced today that results of a phase III clinical trial show drotrecogin alfa --proposed brand name, zovant--reduced the relative risk of death from sepsis with associated acute organ dysfunction (known as severe sepsis) by 19.4 percent. The new data, published today on The New England Journal of Medicine's website (, are from the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial.

Sepsis is a syndrome characterized by an overwhelming systemic response to infection, which can rapidly lead to organ dysfunction and ultimately death. Sepsis may cause multiple organs in the body to fail and may trigger the onset of both abnormal clotting and bleeding. Every day, sepsis results in the death of more than 1,400 people worldwide and is the leading cause of death in noncoronary intensive care units. The Estimated Costs Associated With The Treatment Of Patients With Sepsis Are $17 Billion Annually In The United States.(1) Currently, There Is No Drug Therapy Approved Specifically For The Treatment Of Severe Sepsis.

"The data suggest that one in five people who would have died from severe sepsis survived due to Zovant. We are extremely encouraged by Zovant's potential to help so many who might otherwise succumb to the ravages of sepsis," said August M. Watanabe, M.D., executive vice president, science and technology, for Lilly. "The data give us hope that this truly innovative biotech product, if approved, may help a wide variety of sepsis patients."

Zovant is a recombinant version of naturally occurring activated protein C, and study data indicate it may help balance many of the major forces behind sepsis, including inflammation and clotting in the blood vessels. In June 2000, enrollment in the PROWESS trial was stopped early at the recommendation of an independent Data and Safety Monitoring Board when an interim analysis indicated that the placebo-controlled trial results met the prespecified criteria for reduced mortality among patients treated with Zovant versus those treated with placebo.

The results of PROWESS will also be presented on Feb. 11 at the Society of Critical Care Medicine's 30th International Educational and Scientific Symposium in San Francisco.

"Sepsis strikes hard and takes lives quickly -- three of ten people in the trial died within only a month using the current standard of care. It's exciting to think that Zovant may improve the chances of survival from a syndrome that is so deadly," stated lead clinical investigator for the trial Gordon Bernard, M.D., associate director of the Division of Allergy, Pulmonary and Critical Care z Medicine, Vanderbilt University Medical Center. "After more than 20 investigational compounds studied over the years have failed to produce a specific treatment for sepsis, the Zovant trial results are a real breakthrough."

PROWESS Study Results

PROWESS was a perspective, double-blind, placebo-controlled trial investigating the use of Zovant in patients who had sepsis with at least one associated organ dysfunction. The trial included 1,690 patients from 11 countries who were randomized to receive either placebo (n=840) or Zovant (n=850). The primary endpoint of the study was 28-day all-cause mortality.

Trial data analysis showed a highly statistically significant reduction in the relative risk of mortality of 19.4 percent (p-value = 0.005) for those treated with Zovant, which was administered as a continuous infusion of 24 micrograms per kilogram per hour for 96 hours compared with those patients receiving placebo. The mortality rates were 24.7 percent among Zovant-treated patients versus 30.8 percent among patients treated with placebo. The response to Zovant was consistent across almost all patient subgroups in the clinical trial. Zovant increased the odds of survival by 38.1 percent.

The absolute risk reduction in mortality associated with Zovant was observed within days of treatment and continued to increase throughout the remainder of the study period.

Patients enrolled in the trial had a mean age of 60.5 years old. Approximately 75 percent of the patients had two or more acute organ dysfunctions associated with their sepsis. The primary sites of the infection were the lung (53.6 percent) and abdomen (19.9 percent).

According to The New England Journal of Medicine article about the study, Zovant had an impact regardless of whether patients were protein C deficient. The data suggest that Zovant has pharmacologic effects that go beyond simply replacing a body's activated protein C and that protein C measurements are not needed to determine if a patient would benefit from Zovant.

In the PROWESS study, the administration of Zovant was not associated with an increased rate of drug-related complications other than bleeding. Serious bleeding events were the most common serious adverse event associated with Zovant therapy (3.5 percent for Zovant-treated patients verses 2 percent in placebo-treated patients), but the difference did not reach statistical significance. Serious bleeding events occurred in both treatment groups mainly among a small percentage of patients predisposed to bleeding.

Lilly applied for regulatory approval of Zovant in the United States, European Union and Australia.

Eli Lilly and Company, 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., Eli Lilly and Company provides answers -- through medicines and information -- for some of the world's most urgent medical needs.

This news release contains forward-looking statements that reflect management's current beliefs about the potential for Zovant in the treatment of severe sepsis. However, as with any pharmaceutical under development, there are significant risks and uncertainties in the process of development and regulatory review. There are no guarantees that future clinical trials will confirm the results reported in this release or that the product will receive regulatory approvals or prove to be commercially successful. For further discussion of these and other risks and uncertainties, see the company's most recent Form 10-Q filing dated November 2000.

(1.) Calculated on data from Linde-Zwirble. Age-specific incidence and outcome of sepsis in the U.S. Critical Care Medicine. 1999;27:1-9 (supplement, p A33).

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