FDA Approves Zyprexa for Bipolar Disorder

    Date: January 15, 2004                                                         

For Release: Immediately

Refer to: Marni Lemons

317-433-8990

           FDA Approves Zyprexa®for Maintenance of Bipolar Disorder            

First Atypical Antipsychotic Approved for Treatment of Bipolar Mania Is First
Mania Treatment in 30 Years to Receive Additional Approval for Bipolar
Maintenance

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INDIANAPOLIS, January 15, 2004 -The U.S. Food and Drug Administration (FDA) has
approved Zyprexa® (olanzapine) for maintenance in the treatment of bipolar
disorder, Eli Lilly and Company announced today. This FDA approval recognizes
that Zyprexa is an effective treatment to delay relapse into either mania or
depression in patients with bipolar disorder. Zyprexa is the first treatment in
nearly 30 years to be recognized by the FDA as a treatment for both acute mania
and maintenance treatment in bipolar disorder.

"Bipolar disorder is a serious condition that can be difficult to treat. For
those who achieve stability on existing medications, relapse of symptoms is all
too common," said Frederick K. Goodwin, MD, Director, Center on Neuroscience,
Medical Progress and Society, at the George Washington University Medical
Center, Washington, D.C. "It is good news that the FDA has now approved Zyprexa
as a new tool for physicians to use to delay relapse and prolong periods of
stability and wellness."

Zyprexa was approved by the FDA in 2000 for the short-term treatment of acute
mixed or manic episodes associated with bipolar disorder and is the first
medication approved to both treat acute mania and delay relapse of symptoms
associated with bipolar disorder since lithium received approval from the FDA
in 1974. In addition, the FDA recently approved Symbyax (tm) for the treatment of
bipolar depression. Symbyax combines the active ingredients in Zyprexa and
Prozac®, and is the first and only FDA-approved treatment for this devastating
and difficult-to-treat phase of bipolar disorder.

Zyprexa Delayed Relapse Into Both Mania and Depression in Clinical Trials

The new indication is based on data from a double-blind, placebo-controlled
study that showed time to relapse of either mania or depression was
significantly longer for Zyprexa patients than patients treated with placebo.
Zyprexa-treated patients had a significantly lower rate of either a mania (16.4
percent for Zyprexa versus 41.2 percent for placebo) or depression relapse
(34.7 percent for Zyprexa versus 47.8 percent for placebo).

"We believe that physicians are looking for treatments, like Zyprexa, that
demonstrate that they can effectively delay relapse, not only into the manic
phase, but also into the depressive phase of bipolar disorder," said Mauricio
Tohen, MD, Dr. P.H., Lilly clinical research fellow, Lilly Research
Laboratories and Zyprexa product team leader. "This new indication provides a
treatment option to clinicians and patients that is dependable in treating both
acute manic episodes and delaying new episodes. Longer stable periods may
provide greater opportunities for clinicians to work with their patients on
improving work or family life."

In the placebo-controlled study, common and significant adverse events for the
Zyprexa patients were weight gain, fatigue and inner and outer restlessness
(akathisia).

About Bipolar Disorder

Bipolar disorder, also known as manic-depressive illness, is a complex mental
illness characterized by debilitating swings in mood. These swings range from
manic episodes, marked by abnormal euphoria, elation and irritability, to
episodes of deep depression, marked by extreme sadness and difficulty
functioning, These periods of illness are interspersed with periods of normal
mood. Although a lifelong illness, bipolar disorder typically emerges in
adolescence or young adulthood, and episodes continue intermittently throughout
life.

More than 2.5 million Americans live with a diagnosis of bipolar disorder but
recent research indicates the real number may be as high as 10 million. The
results of untreated bipolar diso rder can be catastrophic. According to the
National Institute of Mental Health, nearly one in every five people with the
illness ends their life by suicide. The World Health Organization estimates
that bipolar disorder is the sixth leading cause of disability in the world.

During relapse into mania or depression, people with bipolar disorder may
experience disruptions in relationships and jobs, suffer feelings of failure or
become suicidal. Recurring relapse may lead to both a worsening of the disease
itself and may contribute to more frequent episodes of relapse.

Important Information About Zyprexa and Symbyax
In addition to the newly approved indication, Zyprexa is indicated in the
United States for the short-term and long-term treatment of schizophrenia, and
either alone or in combination with lithium or valproate (Depakote®, 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 12.5 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 atypicals should 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 not been
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.

Full prescribing information is available at www.zyprexa.com.

Symbyax is indicated in the United States for the treatment of depressive
episodes associated with bipolar disorder.

The most common adverse events reported in patients taking Symbyax in clinical
trials was drowsiness. Other common events noticed in clinical trials were
weight gain, increased appetite, feeling weak, swelling, tremor, sore throat,
and difficulty concentrating.

Hyperglycemia, in some cases associated with ketoacidosis, coma or death, has
been reported in patients treated with atypical antipsychotics, including
olanzapine, and concomitant olanzapine and fluoxetine. 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 atypicals should 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.

Although Symbyax is not approved for elderly patients with dementia it is
important to note the label for Symbyax includes a warning for patients in this
population. 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 clinical
trials for olanzapine, an active ingredient in Symbyax. In fact, Symbyax has
not been studied in elderly patients with dementia, nor do we expect Symbyax to
be used to treat these patients.

Symbyax may induce orthostatic hypotension (a drop in blood pressure when
standing up), associated with dizziness, speeding or slowing of heart rate, and
in some patients, fainting, especially during initial therapy.

Symbyax prescribing should be consistent with the need to minimize the risk of
neuroleptic malignant syndrome, tardive d yskinesia, and orthostatic
hypotension.

Symbyax should not be administered until at least two weeks have passed since
discontinuing an MAO inhibitor, and an MAO inhibitor is contraindicated for at
least five weeks after discontinuation with Symbyax. Thioridazine should not be
administered with Symbyax or within a minimum of 5 weeks after discontinuing
Symbyax. Symbyax should be discontinued immediately if rash or other possibly
allergic phenomena appear for which an alternative explanation cannot be
identified.

Due to the cyclical nature of bipolar disorder, patients should be monitored
for the signs of mania and hypomania during treatment with Symbyax.

Patients should inform their physicians if they are taking Zyprexa, Prozac,
Sarafem or fluoxetine.

Full prescribing information is available at www.symbyax.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 .

This press release contains forward-looking statements about the potential of
Zyprexa for maintenance treatment of bipolar disorder 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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