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CHMP Recommends Approval of Olanzapine Long-acting Injection for Maintenance Treatment of Schizophrenia in Europe

INDIANAPOLIS, September 26, 2008 /PRNewswire-FirstCall/ -- The Committee for Medicinal Products for Human Use (CHMP) has recommended European approval of Olanzapine Long-acting Injection (LAI), known in Europe by the trade name Zypadhera(TM), for maintenance treatment of adult patients with schizophrenia sufficiently stabilized during acute treatment with oral olanzapine, Eli Lilly and Company (LLY) announced today.

The CHMP's positive opinion is now referred for final action to the European Commission, which grants approval in the European Union. The Commission usually makes a decision on CHMP recommendations within two to three months.

Olanzapine LAI is an investigational formulation that 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. Earlier this month, olanzapine LAI was approved for use in New Zealand. Independent regulatory reviews of olanzapine LAI applications for schizophrenia are ongoing in the United States, Canada, Australia and other countries.

Since olanzapine was introduced in 1996, it has been prescribed to more than 26 million people worldwide. Long-acting injectables have been associated with improved treatment for patients who struggle with adherence to oral medications.(i)

"Because of the chronic and severe nature of schizophrenia, persistent challenges with adherence and the limited number of depot formulations available, we believe that olanzapine LAI has the potential to become a valuable treatment option for patients," said David McDonnell, M.D., clinical research physician at Lilly. "We look forward to making olanzapine LAI available in the European Union in the near future."

The CHMP opinion was 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. In these trials, olanzapine LAI was found to be similar to olanzapine oral in terms of rate of symptom exacerbation and showed a similar safety profile as the oral formulation with the exception of injection-related events, including Post-Injection Delirium/Sedation Syndrome (PDSS).(iv)

As of August 31, 2008, across all clinical trials, PDSS events, including a range of symptoms of sedation (from mild in severity to unconsciousness) and/or delirium (including confusion, disorientation, agitation, anxiety and 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 in Europe, Lilly has proposed a comprehensive risk minimization plan for identifying and managing PDSS. 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.

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 due to convenience 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.(vii) 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.(viii) 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.(ix)

About Schizophrenia

Schizophrenia is a severe and debilitating illness with such symptoms 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.(x) In addition to these symptoms, patients with schizophrenia are at greater risk for medical comorbidities than the general population.

About Oral Zyprexa

Zyprexa is indicated in the United States for the short- and long-term treatment of schizophrenia, acute mixed and manic episodes of bipolar disorder, and maintenance treatment of bipolar disorder. Since Zyprexa was introduced in 1996, it has been prescribed to more than 26 million people worldwide. Zyprexa is not approved for patients under 18 years of age.

ZYPREXA IS NOT APPROVED FOR THE TREATMENT OF PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS TREATED WITH ATYPICAL ANTIPSYCHOTIC DRUGS ARE AT AN INCREASED RISK OF DEATH COMPARED WITH THOSE PATIENTS TAKING A PLACEBO.

In addition, compared to elderly patients with dementia-related psychosis taking a placebo, there was a significantly higher incidence of cerebrovascular adverse events in elderly patients with dementia-related psychosis treated with Zyprexa.

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including Zyprexa.

While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or who have borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Persons with risk factors for diabetes who are starting on atypical antipsychotics should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Significant, and sometimes very high, elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.

Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.

As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with Zyprexa. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite and tremor.

Full prescribing information, including a boxed warning, is available at www.zyprexa.com .

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.

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.com

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.

(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. May 2008.

(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 Schizophrenia International Research Society Meeting. June 21-25, 2008.

(iv) 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 Schizophrenia International Research Society Meeting. June 21-25, 2008.

(v) McDonnell D., Sorsaburu S., Brunner E., Detke H., Andersen S., Bergstrom R., Mitchell M., Ogle K., Watson S., Corya S. Post-Injection Delirium/Sedation Syndrome Observed with Olanzapine Long-Acting Injection. Data Presented at European College of Neuropsychopharmacology Meeting. August 30-September 3, 2008.

(vi) Falkai P., Wobrock T., Lieberman J., Glenthoj B., Gattaz W.F., Moller H.J & Wfsbp Task Force On Treatment Guidelines For Schizophrenia. The World Journal of Biological Psychiatry, 2006; 7(1): 5/40

(vii) 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.

 

               (viii) Kane J.M et al. Guidelines for depot antipsychotic

treatment in schizophrenia. European Neuropsychopharmacology, Volume 8, Number 1, 1 February 1998, pp. 55-66(12). p. 58.

(ix) 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.

(x) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fourth edition, 2000, pp. 298.

 

CONTACT: Janell Smith, +1-317-277-9603 (office), +1-317-358-5396 (mobile),, or Charlie McAtee, +1-317-277-1566 (office),+1-317-997-1627 (mobile), , both of Eli Lilly and Company smithja@lilly.com mcateech@lilly.com

Ticker Symbol: (:LLY)

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Posted: September 2008


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