Lilly Plans New Clinical Trial of Xigris(R)

Lilly Plans New Clinical Trial of Xigris(R)

February 26, 2007

Trial will help better identify appropriate patient, define
the benefit-risk profile in this population

    INDIANAPOLIS, Feb. 26 /Xinhua-PRNewswire/ -- Eli Lilly
and Company (NYSE: LLY) today announced plans for a new
clinical study of Xigris(R) (drotrecogin alfa [activated]).
The trial is designed to help clinicians better identify
severe sepsis patients at high risk of death who are more
likely to benefit from this novel therapy and to further
clarify the drug's benefit/risk profile.  The new trial
initiative follows discussions with the European Medicines
Agency (EMEA) in the context of its fourth annual license
reassessment for Xigris. 

    (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO)

    "Advancements made in sepsis care over the past
five years, and ongoing scientific questions surrounding
appropriate patient selection for Xigris and about severe
sepsis treatment in general make this an opportune time for
a new Phase III placebo-controlled study of Xigris,"
said J. Anthony Ware, M.D., vice president, Lilly Research
Laboratories and global platform leader for cardiovascular
and acute care. "The trial may provide additional
scientific insights and potential patient benefits." 


    Xigris was licensed in the EU in August 2002 under
exceptional circumstances, which establishes an annual
review. During each reassessment, the Committee for
Medicinal Products for Human Use (CHMP) reviews all
existing data. In discussions, Lilly committed to conduct a
new placebo-controlled clinical trial to help refine
appropriate patient identification for treatment with
Xigris.  Commercial Xigris will remain available to
physicians for treatment of severe sepsis patients within
the currently approved label during the course of the
trial. 

    In the United States, where Xigris is licensed for
adult patients with severe sepsis (sepsis associated with
acute organ dysfunction) at high risk of death, the federal
Food and Drug Administration does not annually reassess
licensing. 

    Lilly's medical team is working with medical experts in
Europe and the United States to develop a protocol for the
international trial involving Xigris, with the primary
endpoint being 28-day all-cause mortality. Lilly estimates
the trial will begin enrolling patients during the first
quarter of 2008 and take approximately two and a half years
to complete. 

    PROWESS(i) - Recombinant Human Activated PROtein C
Worldwide Evaluation in Severe Sepsis - the pivotal Phase
III registration trial for Xigris, was initiated in July
1998. Enrollment was suspended at the second interim
analysis in June 2000 because Xigris demonstrated a
significant survival benefit that exceeded the
prospectively set stopping rules.  The trial showed a
relative risk reduction in mortality among high risk
patients by 29 percent. Mortality rates were 30.9 percent
among drotrecogin alfa (activated)-treated patients vs.
43.7 percent among patients treated with placebo
(p=0.0002).  In patients with multiple organ dysfunction,
mortality rates were 26.5 percent among drotrecogin alfa
(activated)-treated patients vs. 33.9 percent in patients
treated with placebo (p=0.006).  PROWESS was the first
large severe sepsis trial to meet the primary endpoint of a
significant reduction in mortality and led to approval of
Xigris in more than 50 countries globally.

    The new trial will be conducted in patients within the
currently indicated population (adults with severe sepsis
at high risk of death) and utilize the current standard of
care for severe sepsis. It will differ from PROWESS in that
it will set further parameters for patient identification
and evaluation to identify patients early in the course of
sepsis, and to ensure appropriate and adequate patient
selection and safety assessments for those receiving the
drug.    

    Xigris is the only approved pharmaceutical therapy
specifically indicated in Europe for the treatment of adult
patients with severe sepsis with multiple organ failure when
added to best standard care. The use of Xigris should be
considered mainly in situations when therapy can be started
within 24 hours after the onset of organ failure. In the
United States Xigris is indicated to reduce mortality in
adult patients with severe sepsis (sepsis associated with
acute organ dysfunction) at high risk of death. 

    "Lilly stands firmly behind the PROWESS trial,
which led to the approval of Xigris in more than 50
countries," said Mark D. Williams, M.D., medical
director for Xigris. "This new study will focus on
helping physicians identify the optimal patient for Xigris
therapy by further clarifying the benefit-risk profile of
this novel therapy." 

    Several post-marketing studies have provided
significant insights into severe sepsis pathophysiology and
treatment with Xigris. Lilly is committed to applying this
learning in this new clinical trial with these indicated
patients -- the adult patient with severe sepsis at high
risk of death, Williams said. 

    In addition to the new placebo-controlled study, a
Phase II Xigris clinical trial began in November 2006.
RESPOND - Research Evaluating Serial Protein C levels in
severe sepsis patients ON Drotrecogin alfa [activated] - is
designed to tailor the dose and duration of Xigris based
upon serial Protein C levels. Data from this trial could
advance Xigris therapy by using a biomarker such as Protein
C to provide the right dose of Xigris to the right patient
at the right time, said Williams. Five hundred patients are
being enrolled at 50 sites in 11 countries for the trial.

    About Severe Sepsis

    Sepsis is a common, deadly and under-diagnosed disease
that claims approximately 1,400 lives worldwide each day. 
Severe sepsis often develops as a complication after common
illnesses such as pneumonia, and bacterial infections. 
Annually, there are approximately 88 cases of severe sepsis
per 100,000 people in Europe and 750,000 cases in the United
States, largely as a consequence of rapid organ failure
during the most life-threatening stage of the illness --
the first 28 days.(ii)(iii)(iv) 

    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 mg 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). 

    Bleeding is the most common serious adverse effect
associated with Xigris therapy.  In PROWESS, a Phase III
study, serious bleeding events were observed during the
28-day study period in 3.5 percent of Xigris-treated and
2.0 percent of placebo-treated patients.  The difference in
serious bleeding occurred primarily during infusion.  Each
patient being considered for therapy with Xigris should be
carefully evaluated and anticipated benefits weighed
against potential risks associated with therapy.  For full
safety information including contraindications and
warnings, please see Xigris Prescribing Information, which
can be obtained by visiting http://www.Xigris.com .

    Lilly, a leading innovation-driven corporation, is
developing a growing portfolio of first-in-class and
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.  

    P-LLY

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

    i The Recombinant Human Activated Protein C Worldwide
Evaluation in Severe Sepsis (PROWESS) study was initiated
in July 1998. Enrollment was suspended at the second
interim analysis in June 2000 because Xigris demonstrated a
significant survival benefit that exceeded the prospectively
set stopping rules. Analysis indicated a statistically
significant 29% relative reduction in risk of death among
high-risk (APACHE II score greater than or equal to 25)
patients (P=0.0002). In these patients, survival rates were
69% for Xigris patients, compared to 56% for standard
therapy patients at 28 days. The difference in survival was
sustained through 2.5 years of follow-up.
    ii Angus DC et al. Crit Care Med 2001; 29,: 1303-10
    iii Davies A et al. A European estimate of the burden
of disease in ICU. In preparation.
    iv Bone RC et al. Chest 1992; 101:1644-55


    For more information, please contact:

    Joedy Isert 
    Eli Lilly and Company
    Tel:  [phone]
    Cell: [phone]


SOURCE  Eli Lilly and Company