Lilly Asserts The New England Journal of Medicine ``Sounding Board'' Opinion Article Attempts to Turn Back the Clock on Care of

     
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( BW)(ELI-LILLY-&-CO)(BC43) Lilly Asserts The New England Journal of
Medicine ``Sounding Board'' Opinion Article Attempts to Turn Back the
Clock on Care of Severe Sepsis Patients

    Business Editors
    UK REGULATORY NEWS

    INDIANAPOLIS--(BUSINESS WIRE)--Sept. 25, 2002--

  In Rare Written Rebuttal, FDA Reaffirms That Xigris(R) Saves Lives

Eli Lilly and Company (NYSE:LLY) today stated that "Risks and Benefits
of Activated Protein C Treatment for Severe Sepsis" (Warren, et al.),
an opinion article published in this week's The New England Journal of
Medicine(a) is without merit.

The four authors' opinions regarding the protocol design and outcomes
from the 1,690-patient Phase III PROWESS trial of Xigris(R)
(drotrecogin alfa (activated)) are based on incomplete information and
contradict the decisions of the multiple independent authorities that
analyzed Xigris clinical data. This includes the U.S. Food and Drug
Administration (FDA), the Centers for Medicare and Medicaid Services
(CMS), regulatory authorities in 11 other countries(1) and, most
recently, the European Committee for Proprietary Medicinal Products
whose positive opinion resulted in Xigris approval in the 15 member
countries it represents.

"Xigris is a proven lifesaving advance for the treatment of adult
patients with life-threatening severe sepsis. To imply otherwise in
the pages of one of the world's most prestigious medical journals --
10 months after the FDA approved this therapy based on the strength of
our clinical data -- attempts to turn back the clock on the treatment
of severe sepsis. The opinion article's assertions serve only to
confuse physicians who are attempting to make the best treatment
decisions for their patients with severe sepsis, " said August M.
Watanabe, M.D., executive vice president, science and technology, for
Lilly.

"Severe sepsis shows no mercy, so I want to offer my patients every
advantage in their struggle to survive. There is no doubt in my mind
that Xigris, when used appropriately, is an unprecedented, lifesaving
advance for this vulnerable patient population," said Greg A. Schmidt,
M.D., professor of clinical medicine, clinical anesthesia, and
critical care, and director of medical intensive care, University of
Chicago.

FDA and CMS Reaffirm Lifesaving Potential of Xigris for Most
Vulnerable Patients

In the same issue of The New England Journal of Medicine, the FDA
rebutted the questions of Warren, et al., point by point, concluding
that the data strongly support that use of Xigris, as labeled, will
save many lives.

Based on the PROWESS trial's results, the FDA approved Xigris in
November 2001 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(2)).

In his Sounding Board response, "Assessing the Use of Activated
Protein C in the Treatment of Severe Sepsis," Jay P. Siegel, M.D.,
director, Office of Therapeutics Research and Review, FDA Center for
Biologics Evaluation and Research, said that extensive review
conducted by the agency -- which also included substantial post hoc
data evaluations following the Xigris Advisory Committee hearing --
confirmed the principal findings of the PROWESS trial. This review
included several specific analyses strongly supporting the conclusion
that a protocol amendment made during the course of the trial did not
affect the study outcome.

Importantly, the FDA also reported in The New England Journal of
Medicine that the most vulnerable severe sepsis patients -- those of
advanced age, those who experience acute physiological changes and
those with chronic health points (a scoring system that assesses
mortality risk) -- are also the patients who benefited the most from
Xigris therapy.

"Xigris data has been favorably reviewed and approved for use in 27
countries to date. Challenging the integrity of the PROWESS trial is
out of step with the majority opinion among regulatory authorities
worldwide. This fact stands on its own," said Watanabe.

"We disagree with the authors' suggestion that we should contemplate
denying severe sepsis patients fighting for their lives access to an
FDA-approved therapy in order to replicate the proven findings from
the largest trial of its kind ever conducted. In our viewpoint, that
would be unethical," he said.

In addition, CMS (formerly HCFA) recently selected Xigris as the first
and only medical product to be granted new technology status because
it provides a substantial improvement in treatment for Medicare
patients with life-threatening severe sepsis. Beginning Oct. 1, 2002,
this designation will allow hospitals that use Xigris in the treatment
of Medicare patients with life-threatening severe sepsis to receive
additional reimbursement. In a statement on the decision, Department
of Health and Human Services Secretary Tommy G. Thompson said, "In an
era of unprecedented scientific breakthroughs, we must do all we can
to ensure that all patients have access to the latest in medical
innovations."

The Critical Care Perspective

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 were limited to 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.

More 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 or equal to 25), was reduced by 29
percent (p=0.002) in the PROWESS (Recombinant Human Activated Protein
C Worldwide Evaluation in Severe Sepsis) trial involving 1,690
patients.

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, and 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.

Certain of the matters discussed herein with respect to clinical
studies and Lilly's products may constitute forward-looking statements
within the meaning of the Private Securities Litigation Reform Act of
1995. Such forward-looking statements are based on current
expectations, estimates and projections about the industry, management
beliefs and certain assumptions made by management. Investors are
cautioned that matters subject to forward-looking statements involve
risks and uncertainties, including economic, competitive,
governmental, technological and other factors discussed in the
company's filings with the Securities and Exchange Commission, which
may affect the business and prospects of the company. More
specifically, there can be no assurance that this product will achieve
commercial success or that competing products will not preempt any
market opportunity that might exist for the product.

Xigris(R) (drotrecogin alfa (activated), Lilly) DR24933

References

(a) The New England Journal of Medicine, Sept. 26, 2002, Vol. 347,
    No.13, pp.1027-1030.

(1) Argentina, Australia, Colombia, India, Israel, Mexico, Peru,
    Romania, Singapore, South Africa, Switzerland

(2) Acute Physiology and Chronic Health Evaluation Score

(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: 00000841
   Time of Receipt (offset from UTC): 20020925T203430+0100

    --30--mj/in*

    CONTACT: Eli Lilly and Company
             Dan Collins, 317/277-2688
             Anne Griffin, 317/276-3254

    KEYWORD: INDIANA UNITED KINGDOM INTERNATIONAL EUROPE
    INDUSTRY KEYWORD: PHARMACEUTICAL MEDICAL PRODUCT
    SOURCE: Lilly (Eli) & Co

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