INDIANAPOLIS, Jan. 7 /PRNewswire-FirstCall/ -- Eli Lilly and Company
(NYSE: LLY) announced today that it received a complete response letter from
the U.S. Food and Drug Administration (FDA) for olanzapine long-acting
injection (LAI) for acute and maintenance treatment of schizophrenia in
adults. Lilly is continuing to work with the agency on the new drug
application (NDA).
The FDA does not require any additional clinical trials for the continued
review of the NDA. Per the agency's request, Lilly is preparing a proposed
Risk Evaluation and Mitigation Strategy (REMS), which will be submitted in the
near future.
"We cannot speculate on the timing of a potential decision, but remain
confident that, if approved, the long-acting depot formulation of olanzapine
will offer an important option for treating this devastating and chronic
illness," said Todd Durell, M.D., associate medical director for U.S.
neuroscience for Lilly.
This treatment has been approved for use in the European Union and New
Zealand under the trade name Zypadhera(TM). Independent regulatory reviews are
ongoing in 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 if it is determined that a depot formulation
is necessary to help with compliance.(1)
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.(2)
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.(3)
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.(4) In addition to
these symptoms, patients with schizophrenia are at greater risk for medical
comorbidities than the general population.
Safety information for Zyprexa
Zyprexa oral is indicated in the United States for the short- and long-
term treatment of schizophrenia, acute mixed and manic episodes of bipolar I
disorder, and maintenance treatment of bipolar disorder.
Olanzapine is not approved for the treatment of patients with dementia-
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related psychosis. Elderly patients with dementia-related psychosis
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treated with antipsychotic drugs are at an increased risk of death.
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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 olanzapine.
Hyperglycemia, in some cases associated with ketoacidosis, coma, or death,
has been reported in patients treated with atypical antipsychotics, including
olanzapine. 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 having borderline increased blood glucose level.
Patients taking olanzapine should be monitored regularly for worsening of
glucose control. 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.
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.
Significant 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.
Olanzapine may induce orthostatic hypotension associated with dizziness,
tachycardia, bradycardia, and in some patients, syncope, especially during the
initial dose-titration period. Particular caution should be used in patients
with known cardiovascular disease, cerebrovascular diseases, or those
predisposed to hypotension.
As with all antipsychotic medications, a rare and potentially fatal
condition known as Neuroleptic Malignant Syndrome (NMS) has been reported with
olanzapine. 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.
Other potentially serious adverse events include seizures, elevated
prolactin levels, elevated liver enzymes, cognitive and motor impairment, body
temperature elevation, and trouble swallowing.
The most common treatment-emergent adverse event associated with oral
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 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 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.
1) 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
2) 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.
3) 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.
4) American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders, fourth edition, 2000, pp. 298.
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