Lilly Plans New Clinical Trial of Xigris(R)

Indianapolis (ots/PRNewswire) -

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

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 regulatory discussions with the European
Medicines Agency (EMEA) in the context of its fourth annual license
reassessment for Xigris.

"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.

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.

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 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

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

Web site: http://www.lilly.com
http://www.Xigris.com

ots Originaltext: Eli Lilly and Company
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Joedy Isert of Eli Lilly and Company, +1-317-276-5592, or cell,
+1-317-997-8544, /Photo: NewsCom:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO , PRN Photo
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