Zypadhera(TM) Receives European Approval for Maintenance Treatment of Schizophrenia (1)

INDIANAPOLIS, December 5 /PRNewswire/ --

Eli Lilly and Company (LLY) has announced that the European Commission has approved the use of Zypadhera (olanzapine powder and solvent for prolonged release suspension for injection, also known as olanzapine long-acting injection) for maintenance treatment of adult patients with schizophrenia sufficiently stabilized during acute treatment with oral olanzapine. This approval, adopted by the EU Commission on 19 November, follows a positive opinion by the European Medicines Agency's (EMEA) Committee for Medicinal Products for Human Use (CHMP) on 25 September 2008.

Olanzapine long-acting injection combines Zyprexa(R) (olanzapine), an atypical antipsychotic, with pamoic acid resulting in a salt that sustains the delivery of olanzapine for a period of up to four weeks. Long-acting injectables have been associated with improved treatment for patients who struggle with adherence to oral medications. (i)

"A primary barrier to the successful treatment of schizophrenia is that patients often relapse because they have trouble taking their medication on a regular basis" said Jean-Pierre Olie, M.D., Sainte-Anne Hospital, France. "Olanzapine long-acting injection is an important addition to the range of treatment options for schizophrenia as long-acting antipsychotics can help patients derive more consistent benefits from their medications, and alleviate the burden on patients to take a daily medication."

This approval is based on a comprehensive data package comprising eight studies, involving 2,054 patients, including a double-blind, placebo-controlled, fixed-dose study (HGJZ)(ii); a double-blind, oral olanzapine-controlled, fixed-dose study (HGKA)(iii); and six open-label studies.(iv) In clinical trials, olanzapine long-acting injection showed efficacy as early as one week without the need for oral supplementation, and was found to have a similar efficacy and safety profile as the oral formulation, with the exception of injection-related events, including Post-Injection Syndrome.(v)

As of 14 October 2008, across all clinical trials, Post-Injection Syndrome events, which include a range of symptoms of sedation (from mild in severity to unconsciousness) and/or delirium (including confusion, disorientation, agitation, anxiety or other cognitive impairment), have been seen in 0.07 percent of injections and 1.4 percent of patients, all of whom have recovered fully.(v)

As part of the marketing authorization, Lilly will implement a comprehensive risk minimization plan for identifying and managing Post-Injection Syndrome. The plan includes a requirement for a post-injection observation period described in the product labeling, and an extensive healthcare provider training and educational program.

Some European countries will launch Zypadhera as early as the first quarter of 2009. Zypadhera was approved for use in New Zealand in September 2008. Additional independent regulatory agency reviews of olanzapine long-acting injection marketing applications are ongoing in the United States, Australia and other countries.

Notes for editors:

About Long-acting Injectable Antipsychotic Medications

The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines state that poor or partial treatment compliance is a major problem in the long-term treatment of schizophrenia. Depot formulations should be considered as a treatment option when a patient expresses a preference for such treatment or if it is determined that a depot formulation is necessary to help with compliance.(vi)

Long-acting antipsychotic formulations have been associated with improved treatment adherence and reduced treatment failures. (i) By administering long-acting medications, healthcare professionals know when patients have received their medication and can immediately detect non-adherence when a patient fails to return for a scheduled injection.(vii) Different from both oral and injected short-acting formulations, long-acting formulations of antipsychotics allow for stable concentrations of the active drug to remain at a therapeutic range for an extended period of time.(i)

About Schizophrenia

Schizophrenia is a severe and debilitating illness with symptoms such as delusions (false beliefs that cannot be corrected by reason), hallucinations (usually in the form of non-existent voices or visions), disorganized speech and severe disorganized or catatonic behavior. These signs and symptoms are associated with marked social or occupational dysfunction. Features of schizophrenia consist of characteristic signs and symptoms that have been present for a significant portion of time during a one-month period, with some signs of the disorder persisting for at least six months.(viii) In addition to these symptoms, patients with schizophrenia are at greater risk for medical comorbidities than the general population.

About Olanzapine

Since olanzapine was introduced in 1996, it has been prescribed to more than 26 million people worldwide. Olanzapine is not recommended for use in patients under 18 years of age.

In Europe, oral olanzapine is indicated for the treatment of schizophrenia. In clinical trials, olanzapine has shown to be effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. It is also indicated for the treatment of moderate to severe manic episodes and, in those patients whose manic episode has responded to olanzapine treatment, it is indicated for the prevention of recurrence in patients with bipolar disorder.

About Lilly

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.co.uk.

P--LLY

This press release contains forward-looking statements about the safety and efficacy of olanzapine long acting injection (LAI) and reflects Lilly's current beliefs. However, as with any investigational pharmaceutical product, there are substantial risks and uncertainties in the process of research, development, regulatory milestones and commercialization. There is no guarantee that olanzapine LAI will be approved for the treatment of schizophrenia or that if approved, it will 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.

References:

i. Maxine X. Patel and Anthony S. David. Why aren't depot antipsychotics prescribed more often and what can be done about it? Advances in Psychiatric Treatment (2005) 11: 203-211.

ii. Lauriello J., Lambert T., Andersen S., Lin D., Taylor C.C., McDonnell D. Olanzapine long-acting injection: an 8-week double-blind, randomized, placebo-controlled study in acutely-ill patients with schizophrenia. Journal of Clinical Psychiatry. 2008; 69(5):790-9.

iii. Detke H., McDonnell D., Kane J., Naber D., Sethuraman G., Lin D. Olanzapine Long-Acting Injection for the Maintenance Treatment of Schizophrenia: A 24-Week, Randomized, Double-Blind Trial. Data presented at the Schizophrenia International Research Society, June 21-25, 2008, Venice, Italy.

iv. Clinical trial studies: LOBE, LOBO, LOBS, HGJW, HGLQ and HGKB (Data on file)

HGKB:

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