Injectable Zyprexa Now Available in First Markets

INDIANAPOLIS, Indiana, February 2 /PRNewswire/ -- - New Option Helps Doctors Rapidly Stabilise Agitated Patients With Schizophrenia and Bipolar Disorder With Low Risk Of Debilitating Side Effects

An injectable form of Zyprexa (olanzapine) is now available, giving doctors a new, rapid-acting treatment option for acutely agitated, non- cooperative patients with schizophrenia and bipolar disorder in hospital emergency rooms or other crisis situations, Eli Lilly and Company announced today. Clinical data demonstrates that injectable Zyprexa(R) enables clinicians to rapidly and dependably relieve patients of the distressing effects of acute agitation with low risk of the debilitating side effects associated with conventional injectable therapies.

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

The injectable intramuscular formulation will be available in France, Australia, Canada, and the United Kingdom early in the first quarter of 2004. Other major markets, including Germany, Spain and Italy, will follow soon thereafter. The formulation is currently under regulatory review in the United States. It will be marketed as Zyprexa IM in Australia, Zyprexa Powder for Solution for Injection in the European Union, and Zyprexa IntraMuscular in Canada and the United States.

An advance supply of Zyprexa IM was given to a small group of clinicians at the psychiatric clinic of the Ludwig Maximilian University in Munich. This historic site is where Emil Kraepelin, considered to be the father of modern psychiatry, conducted the body of his research. Since receiving the medicine, several patients have been successfully treated at this hospital. "We are very pleased with the progress of our patients who have experienced Zyprexa IM. Acute agitation is very distressing, not only for the patient, but for everyone around them. The goal with these patients is to stabilise and help them regain control as soon as possible without causing debilitating side effects, such as acute dystonia. This new medication has allowed us to reduce agitation in as little as 15 minutes," said Professor Hans-Jeurgen Moeller, head of the department of psychiatry at the University. "Initiation of physician-patient communication is essential to achieving treatment goals and Zyprexa IM is an excellent first step to establishing that vital relationship."

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

Acute dystonia is one of the most severe side effects of traditional intramuscular treatments for acute agitation and occurs in about 1 in 10 patients who receive injections of older typical antipsychotic drugs. Characterised by severe muscle spasms in the face and throat that may make patients feel as if they are choking, acute dystonia can frighten patients, impairing their relationships with their psychiatrists and inhibiting them from adhering to the long term treatment vital to preventing relapse.

Seamless Transition to Long-term Therapy

Labelling for injectable Zyprexa specifically states that physicians should transition patients from treatment with the intramuscular formulation to oral Zyprexa as soon as clinically appropriate. "With injectable Zyprexa, physicians have a new option for patients with acute agitation," said Mauricio Tohen, MD, Dr. P.H., Lilly clinical research fellow, Lilly Research Laboratories and Zyprexa product team leader. "We can offer Zyprexa's dependable control from day one and then smoothly, quickly and assuredly transition them to oral Zyprexa for long-term stabilization and protection from disease relapse."

Design and Results of Pivotal Trials

The efficacy and safety of injectable Zyprexa in controlling acute agitation was evaluated in randomised, double-blind, placebo-controlled studies in patients with schizophrenia and bipolar mania. In these studies, the control of agitation with injectable Zyprexa was assessed using several scales, including the Positive and Negative Syndrome Scale Excited Component (PANSS EC).

Results showed that injectable Zyprexa was superior to haloperidol, the most widely used treatment for acute agitation, in reducing agitation at 15, 30, and 45 minutes after injection. Injectable Zyprexa was also statistically superior to placebo after two hours in all four studies.

Safety Information

In these trials, adverse events included somnolence (sleepiness), dizziness and asthenia (weakness). In addition, injectable Zyprexa was associated with infrequent decreases in blood pressure and heart rate that were not clinically significant.

Acute dystonia did not occur in patients treated with injectable Zyprexa, although 6.6 percent of patients treated with haloperidol intramuscular did experience acute dystonia. No adverse event was significantly more frequent for injectable Zyprexa than for haloperidol intramuscular or lorazepam intramuscular. Movement disorders, known as extrapyramidal side effects, were observed at a statistically significant greater frequency with intramuscular haloperidol than with injectable Zyprexa.

In addition, in the four clinical trials using injectable Zyprexa, there was no clinically significant effect on any ECG interval, including QTc. Injectable Zyprexa has not been tested or approved for intravenous (IV) use.

Zyprexa Background

Zyprexa is currently indicated in the European Union (EU), the United States (US), Australia, and Canada for the acute and long-term treatment of schizophrenia, and the short-term treatment of acute manic episodes associated with bipolar disorder. Zyprexa is also indicated in the US for maintenance in the treatment of bipolar disorder. Furthermore, Zyprexa is indicated in Australia for preventing recurrence of manic, mixed or depressive episodes in bipolar I disorder and in the EU for the prevention of recurrence in patients with bipolar disorder whose manic episode has responded to Zyprexa treatment, making it the first atypical antipsychotic to be approved as a mood-stabilising medication. Zyprexa was also the first atypical antipsychotic to prove its long-term effectiveness in patients with schizophrenia. Since Zyprexa was introduced in 1996, it has been prescribed to more than 14 million patients worldwide.

In clinical trials, Zyprexa was generally well tolerated. However, as with all medications, Zyprexa is associated with some side effects, the most common being somnolence and weight gain. Other common treatment-emergent adverse events may include dry mouth, dizziness, asthenia (muscle weakness), akathisia (restlessness), constipation, increased appetite, modest elevations of prolactin, postural hypotension, parkinsonism, oedema, asymptomatic elevations of hepatic transaminase, and tremor. Hyperglycemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported very rarely ( <0.01%). As with other atypicals, appropriate clinical monitoring is advisable particularly in diabetic patients and in patients with risk factors for the development of diabetes mellitus.

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 organisations. Headquartered in Indianapolis, Indiana, 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. 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.

SOURCE Eli Lilly and Company