FDA Approves Injectable Form of Lilly's Zyprexa(R)

FDA Approves Injectable Form of Lilly's Zyprexa(R)
Helps Control Acute Agitation in Schizophrenia and Bipolar Mania 


INDIANAPOLIS, March 30  /PRNewswire-FirstCall/ -- Physicians have a new
fast-acting option for controlling the potentially crippling effects of acute
agitation in patients suffering with schizophrenia and bipolar mania.  The U.S.
Food and Drug Administration (FDA) has approved Zyprexa(R) IntraMuscular
(olanzapine for injection), an injectable form of Lilly's top-selling
medication.

Clinical data demonstrate that Zyprexa IntraMuscular enables physicians to
rapidly and dependably relieve patients of the effects of acute agitation
without many of the debilitating side effects of conventional injectable
therapies.  This new formulationof Zyprexa is the first medication in its class
to be indicated for the treatment of acute agitation associated with both
bipolar mania and schizophrenia.

Sixty-five percent of hospital-based psychiatrists or emergency room physicians
are not satisfied with current intramuscular antipsychotic therapies, primarily
due to side effects that are difficult for patients to tolerate and because
patients must be switched to a different oral therapy once they are stabilized,
according to the Psychiatrist International Project conducted by PKS Research
Partners in February 2004.  In addition, 60 percent of these physicians said
that currently available intramuscular treatments are not adequate in rapidly
calming the agitated patient, which can help the physician to gain a patient's
trust and cooperation.

"Acute agitation is terribly frightening and potentially dangerous for patients
and their caregivers," said Barry Jones, M.D., professor of psychiatry, McMaster
University, Toronto, Canada.  "Zyprexa IntraMuscular enables doctors to help
patients regain control quickly, often with just a single injection.  Further,
because Zyprexa IntraMuscular is not overly sedating, it can help the physician
and patient to begin communicating and working together to achieve treatment
goals and help move the patient's life forward."

Acute Agitation

Acute agitation is a well-recognized behavioral syndrome with a range of
symptoms, including hostility, extreme excitement, poor impulse control, tension
and uncooperativeness.  The syndrome can occur with a number of conditions,
including schizophrenia and bipolar disorder.  Patients suffering from agitation
in its severe forms are usually in an emergency situation and require immediate
treatment to alleviate personal distress and to prevent harm to themselves and
others.

Seamless Transition to Long-term Therapy

FDA labeling for Zyprexa IntraMuscular specifically states that if ongoing
Zyprexa therapy is needed, physicians may transition patients with schizophrenia
and bipolar mania from Zyprexa IntraMuscular to oral Zyprexa as soon as
clinically appropriate.

More than 56 percent of physicians say it is very important or important that an
antipsychotic can be used in an injectable formulation for agitation andan oral
formulation for long-term disease management.

"With Zyprexa IntraMuscular physicians have a new option for treating agitation
in schizophrenia and acute bipolar mania patients," said Mauricio Tohen, M.D.,
Dr.P.H., Lilly Distinguished Scholar. "We can offer highly agitated patients
Zyprexa's dependable control from day one and then smoothly and assuredly
transition them to oral Zyprexa for maintenance treatment."

Design and Results of Pivotal Trials

Zyprexa IntraMuscular's efficacy in controlling acute agitation was evaluated in
three randomized, double-blind, placebo-controlled studies in patients with
schizophrenia (two studies) and bipolar mania (one study).  In these studies,
the control of agitation with Zyprexa IntraMuscular was assessed using several
scales, including the Positive and Negative Symptom Scale Excited Component
(PANSS EC).

Using these scales, Zyprexa IntraMuscular was statistically superior to placebo
in all studies.  On the primary efficacy measure, the PANSS EC,10 mg injections
of Zyprexa IntraMuscular were significantly superior to placebo at the first
time point measured (15 or 30 minutes) after injection.

In the two studies in agitated patients with schizophrenia, Zyprexa
IntraMuscular was compared to haloperidol (Haldol(R)) intramuscular and to
placebo.  The injectable formation of haloperidol, a first generation or
"typical" antipsychotic, has been the standard of care for acutely agitated
patients for many years.

Results showed that both Zyprexa IntraMuscular and haloperidol intramuscular
were superior to placebo.  No adverse event occurred significantly more often
with Zyprexa IntraMuscular than with haloperidol intramuscular.  In fact, in
these studies, painful muscle contractions called dystonia occurred in 6.6
percent of haloperidol intramuscular-treated patients, but did not occur with
Zyprexa IntraMuscular.  Additional side effects that occurred significantly more
often with haloperidol intramuscular -- but not with Zyprexa IntraMuscular --
included tremors, muscle spasms, indigestion and blurred vision.

Zyprexa IntraMuscular was compared to lorazepam (Ativan(R)) intramuscular and to
placebo in the study involving agitated patients with bipolar mania. Lorazepam,
which is an antianxiety,sedative and anticonvulsant medication, also has been
used for decades.  In this study, Zyprexa IntraMuscular was superior to placebo.
 No adverse event occurred significantly more often with Zyprexa IntraMuscular
than with lorazepam intramuscular.  Incontrast, nausea and vomiting were
reported significantly more often in lorazepam intramuscular-treated patients
than in Zyprexa IntraMuscular-treated patients.

Zyprexa Background and Safety Information

In the three Zyprexa IntraMuscular trials, adverse events included drowsiness,
dizziness and muscle weakness.  In addition, Zyprexa IntraMuscular was
associated with infrequent decreases in blood pressure and heart rate that were
clinically manageable.  However, in an open-label clinical pharmacology study in
non-agitated patients with schizophrenia in which the safety and tolerability of
intramuscular olanzapine were evaluated under a maximal dosing regimen (three 10
mg doses administered 4 hours apart), approximately one- third of these patients
experienced a significant orthostatic decrease in systolic blood pressure (i.e.,
decrease greater than or equal to 30 mmHg). The risk for hypotension (low blood
pressure), bradycardia (slowing of heart rate), and sinus pause may be greater
in non-psychiatric patients compared to psychiatric patients who are possibly
more adapted to certain effects of psychotropic drugs.

Oral Zyprexa is indicated in the United States for the short-term and long-term
treatment of schizophrenia, for maintenance in the treatment of bipolar
disorder, and either alone or in combination with lithium or valproate
(Depakote(R), Abbott) for the short-term treatment of acute mixed or manic
episodes associated with bipolar disorder.  Since Zyprexa was introduced in
1996, it has been prescribed to more than 14 million people worldwide.

The most common treatment-emergent adverse event associated with Zyprexa in
placebo-controlled, short-term schizophrenia and bipolar mania trials was
drowsiness.  Other common events were dizziness, weight gain, personality
disorder (COSTART term for nonaggressive objectionable behavior), constipation,
restlessness, episodes of low blood pressure, dry mouth, weakness, upset
stomach, increased appetite, and tremor.  A small number of patients experienced
asymptomatic elevations of certain liver enzymes; none of these patients
experienced jaundice.

Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has
been reported in patients treated with atypical antipsychotics including
Zyprexa.  Assessment of the relationship between atypical antipsychotic use and
glucose abnormalities is complicated by the possibility of an increased
background risk of diabetes mellitus in patients with schizophrenia and the
increasing incidence of diabetes mellitus in the general population.  The
available data are insufficient to provide reliable estimates of differences in
hyperglycemia-related adverse event risk among the marketed atypical
antipsychotics.  All patients taking atypicalsshould be monitored for symptoms
of hyperglycemia.  Persons with diabetes who are started on atypicals should be
monitored regularly for worsening of glucose control; those with risk factors
for diabetes should undergo baseline and periodic fasting blood glucose testing.
 Patients who develop symptoms of hyperglycemia during treatment should undergo
fasting blood glucose testing.

Prescribing should be consistent with the need to minimize the risk of
neuroleptic malignant syndrome, tardive dyskinesia, seizures and low blood
pressure.

In short-term (six-week) acute bipolar mania trials in combination with lithium
or valproate, the most common treatment emergent adverse event associated with
Zyprexa and lithium or valproate was dry mouth.  Other common events were weight
gain, increased appetite, dizziness, back pain, constipation, speech disorder,
increased salivation, amnesia and abnormal burning or tingling of the skin.

Although the efficacy of Zyprexa in elderly patients with dementia has notbeen
established in clinical trials and Zyprexa is not approved for use in this
patient population, it is important to note the label for Zyprexa includes a
warning for elderly patients with dementia.  The warning states that strokes or
mini-strokes (also called transient ischemic attacks or TIAs), including
fatalities were reported in elderly patients with dementia-related psychosis
participating in Zyprexa clinical trials.  In addition, Lilly has completed a
medical review of five placebo-controlled trials in elderly patients with
dementia, and found an increased incidence of mortality from any cause in the
Zyprexa group compared to patients who took placebo (3.5% vs. 1.5%).  In this
review, risk factors that predisposed Zyprexa patients to increased mortality
included age greater than 80 years, sedation, simultaneous use of certain
sedative and anti-anxiety medications (called benzodiazepines) or presence of
pulmonary conditions such as pneumonia.  Lilly is currently addressing this
mortality data with the FDA.

  Full prescribing information is available at http://www.zyprexa.com/ .

  About Eli Lilly and Company


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 http://www.lilly.com/ .

This press release contains forward-looking statements about the potential of
Zyprexa IntraMuscular and reflects Lilly's current beliefs.  However, as with
any pharmaceutical product, there are substantial risks and uncertainties in the
process of development and commercialization.  There is no guarantee that the
product will prove to be commercially successful.  For further discussion of
these and other risks and uncertainties, see Lilly's filings with the United
States Securities and Exchange Commission.  Lilly undertakes no duty to update
forward-looking statements.

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DATASOURCE: Eli Lilly and Company



CONTACT:  Marni Lemons of Eli Lilly and Company, [phone]

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