Lilly Launches World's Largest Severe Sepsis Clinical Trial; 11,000 Patients to be Enrolled in Study of Xigris Use in Patients w

     
BW20020917002273  20020917T133401Z UTC


( BW)(ELI-LILLY-&-CO)(BC43) Lilly Launches World's Largest Severe
Sepsis Clinical Trial; 11,000 Patients to be Enrolled in Study of
Xigris Use in Patients with Low Risk of Death

    Business Editors
    UK REGULATORY NEWS

    INDIANAPOLIS--(BUSINESS WIRE)--Sept. 17, 2002--

Eli Lilly and Company (NYSE:LLY) announced today the launch of the
largest study ever conducted to investigate treatment for severe
sepsis, a devastating syndrome characterized by an overwhelming
systemic response to infection that claims the lives of at least
215,000 Americans each year.

The Phase IV trial, called ADDRESS, (Administration of Drotrecogin
alfa (activated) in Early Severe Sepsis), will study the effectiveness
of Xigris(R) (drotrecogin alfa (activated)) in 11,000 adult severe
sepsis patients who have a lower risk of death. The U.S. Food and Drug
Administration (FDA) approved Xigris in November 2001 for use in adult
severe sepsis patients at high risk of death, (e.g., as determined by
APACHE II).(1)

The primary objective of the ADDRESS trial is to demonstrate that,
compared to placebo and conventional care, Xigris will reduce
mortality at 28 days in adult patients with severe sepsis who have a
lower risk of death. Patients may be considered at lower risk of death
by having a single organ failure, by APACHE score or by their
physician's assessment. In all, 11,000 patients will be enrolled
worldwide at approximately 1,000 clinical trial sites. Roughly half of
the trial subjects will be enrolled in the United States. The ADDRESS
trial is scheduled to conclude in March 2005.

"The start of this study -- the largest severe sepsis trial ever - is
very meaningful for patients and physicians," said the trial's
principal investigator Edward Abraham, M.D., Professor and Head of the
Division of Pulmonary Sciences and Critical Care Medicine at the
University of Colorado Health Sciences Center. "In clinical trials and
in clinical practice, Xigris has proven its ability to save the lives
of patients with severe sepsis at high risk of death. Through ADDRESS,
we are eager to explore Xigris' potential to also reduce mortality in
this vulnerable patient population with lower risk of death."

The FDA granted marketing approval for Xigris based upon the results
of the Phase III PROWESS trial demonstrating an overall 19.4 percent
reduction in mortality, which involved 1,690 patients with severe
sepsis. PROWESS demonstrated that Xigris reduced the relative risk of
death by 29 percent for severe sepsis patients at high risk of death.
As PROWESS results were inconclusive in severe sepsis patients at
lower risk of death, this patient population is now being studied by
the ADDRESS trial.

Since its approval by the FDA, Xigris also has received approval from
regulatory agencies in 28 other countries,(2) including, most
recently, the 15 member states of the European Union. In October, the
Centers for Medicare and Medicaid Services (CMS) will begin allowing
hospitals that use Xigris in treating Medicare patients to receive
additional reimbursement under the provisions of the Benefits
Improvement Act of 2000.

"The ADDRESS trial is a major step in our ongoing commitment to
improving medical care for patients with severe sepsis," said William
Macias, M.D., Xigris Medical Director at Eli Lilly and Company. "With
cases of severe sepsis climbing dramatically, early detection and
effective medical intervention are crucial to dealing with this
too-often-fatal condition. Given the current lack of effective
therapies for lower-risk severe sepsis patients, we are hopeful this
trial will demonstrate how Xigris may advance the standard of clinical
care for a greater number of individuals afflicted with severe
sepsis."

About Severe Sepsis

Severe sepsis occurs when an infection (bacterial, viral, fungal or
parasitic) - often the result of trauma, surgery, burns or cancer -
triggers a cascade of immune system responses that can lead to acute
organ dysfunction and often death. One of every three sepsis patients
will die within one month. Before FDA approval of Xigris, treatment
options for patients with severe sepsis included treatment for the
infection and supportive care, such as mechanical ventilation, and
kidney dialysis. When added to conventional care, Xigris can further
decrease mortality in these severely ill patients.

The number of severe sepsis cases has been rising significantly over
the past few decades - growing nearly 300 percent over the past 25
years(3) - and the incidence is expected to continue climbing. This
year alone, more than 750,000 Americans will develop severe sepsis,
and at least 215,000 of them will die from the disorder - about as
many as die as a result of an acute heart attack. Research suggests
more than 6.8 million new cases of severe sepsis will occur in the
United States between 2003 and 2010. Approximately 95 percent of these
will be among people who are 65 or older with the majority of these
cases - nearly 60 percent - occurring among people aged 65-75.(4)
Nonetheless, sepsis can strike regardless of a person's age.

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 FDA approved the use of 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 25) was reduced by 29 percent in the
PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in
Severe Sepsis) trial involving 1,690 patients (p=0.002).

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. In addition
to the ADDRESS trial investigating the use of Xigris in lower-risk
patients, Lilly is undertaking trials of the use of Xigris in children
with severe sepsis, and the optimal use of low-dose heparin with
Xigris. These trials are part of the post-marketing studies that Lilly
agreed to conduct when Xigris was approved.

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.

This news release contains forward-looking statements that reflect
management's current beliefs about the potential for Xigris in the
treatment of lower-risk severe sepsis patients. However, as with any
pharmaceutical product, there are significant risks and uncertainties
in the process of development and regulatory review. There are no
guarantees that the ADDRESS trial will be successful or that
regulatory approvals will be received for an expanded indication. For
additional information about the factors that affect the company's
business, please see Exhibit 99 to the company's latest Form 10-Q. The
company undertakes no duty to update forward-looking statements.

(1) Acute Physiology and Chronic Health Evaluation Score.

(2) Argentina, Australia, Colombia, Iceland, India, Israel, Mexico,
Norway, Peru, Romania, Singapore, South Africa, Switzerland and the 15
member states of the European Union.

(3) Society of Critical Care Medicine Web site
(www.sccm.org/pressroom/sepsis_info.html)

(4) Angus D., et al. Epidemiology of severe sepsis in the United
States: analysis of incidence, outcome, and associated costs of care.
Crit Care Med 2001; 29(7): 1303-1310.

   Short Name: Lilly (Eli) & Co
   Category Code: MSC
   Sequence Number: 00000795
   Time of Receipt (offset from UTC): 20020917T134415+0100

    --30--djl/cl* mh/uk*

    CONTACT: Eli Lilly and Company
             Anne Griffin, 317/276-3254
             Dan Collins, 317/277-2688
                        or
             Lilly Global
             Doyia Chadwick, 317/433-9271

    KEYWORD:  INDIANA UNITED KINGDOM INTERNATIONAL EUROPE
    INDUSTRY KEYWORD:  MEDICAL BIOTECHNOLOGY PHARMACEUTICAL
    SOURCE:  Eli Lilly and Company

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