INDIANAPOLIS, Sept. 26 /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 http://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 http://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. (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company 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
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