Zypadhera(TM) Receives Positive Opinion from the European Committee for Medicinal Products for Human Use (CHMP) for Maintenance Treatment of Schizophrenia



    INDIANAPOLIS, Sept. 26 /CNW/ - The Committee for Medicinal Products for
Human Use (CHMP) has issued a positive opinion recommending approval 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, Eli Lilly and Company (LLY) announced
today.
    The opinion issued by the CHMP will need to be ratified by the European
Commission before the new indication is considered approved. The Commission
usually makes a decision within two to three months of a CHMP recommendation.
    Olanzapine long-acting injection (LAI) is an investigational formulation
that combines 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).
    "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 long-acting injection has the potential
to become a valuable treatment option for patients," said David McDonnell,
M.D., clinical research physician at Lilly.
    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(iv). In these trials, olanzapine long-acting injection 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 olanzapine LAI Post-Injection Syndrome(v).
Additionally, the trials showed that olanzapine long-acting injection
separated from placebo as measured by total PANSS score reduction over 8 weeks
of treatment, and a drug effect that was observed as early as one week from
the first injection(vi). Olanzapine long-acting injection was studied as a
once-every-four-week and a once-every-two-week injection, without the need for
oral antipsychotic supplementation.
    As of August 31, 2008, across all clinical trials, olanzapine LAI
Post-Injection Syndrome 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(vii).
    As part of the marketing authorization, Lilly has proposed a
comprehensive risk minimization plan for identifying and managing olanzapine
LAI 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.
    Earlier this month, Zypadhera 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.

    
    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.(viii)
    Long-acting antipsychotic formulations have been associated with improved
treatment adherence and reduced treatment failures.(ix) 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.(*) 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.(xi)

    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.(xii) 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, olanzapine is indicated for schizophrenia and in clinical
trials, it has shown to be effective in maintaining the clinical improvement
during continuation therapy in patients who have shown an initial treatment
response. It also is 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.

    SAFETY INFORMATION

    Hyperglycaemia and/or development or exacerbation of diabetes
occasionally associated with ketoacidosis or coma has been reported rarely,
including some fatal cases. In some cases, a prior increase in body weight has
been reported, which may be a predisposing factor. Appropriate clinical
monitoring is advisable, particularly in diabetic patients and in patients
with risk factors for diabetes mellitus for which regular glucose control is
recommended.
    Undesirable alterations in lipids have been observed in
olanzapine-treated patients in placebo-controlled clinical trials. Mean
increases in fasting lipid values (total cholesterol, LDL cholesterol, and
triglycerides) were greater in patients without evidence of lipid
dysregulation at baseline. Lipid alterations should be managed as clinically
appropriate, particularly in dyslipidemic patients and in patients with risk
factors for the development of lipids disorders.
    The proportion of patients who had adverse, clinically significant
changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides
increased over time. In adult patients who completed 9-12 months of therapy,
the rate of increase in mean blood glucose slowed after approximately 4-6
months.
    As with all antipsychotic medications, a rare and potentially fatal
condition known as Neuroleptic Malignant Syndrome (NMS) has been reported
rarely 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 increases as the duration of treatment. If signs and symptoms of
TD are observed a dose reduction or discontinuation should be considered and
it should be noted that the symptoms can temporally deteriorate or even rise
after discontinuation.
    Other potentially serious adverse events include low blood pressure,
seizures, elevated prolactin levels, elevated liver enzymes, thromobembolism,
neutopenia, sweating, insomnia, tremor, anxiety, nausea, or vomiting.
    Olanzapine should not be used in patients who have a hypersensitivity to
the drug nor those with narrow angle glaucoma. It should not be used to treat
dementia-related psychosis and/or behavioural disturbances because of an
observed increase in death and cerebrovascular accident. It should also not be
used in the treatment of dopamine agonist associated psychosis in patients
with Parkinson's disease.
    The most frequently (seen in (greater than)/= 1% of patients ) reported
adverse reactions associated with the use of olanzapine in clinical trials
were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol,
glucose and triglyceride levels, glucosuria, increased appetite, dizziness,
akathisia, parkinsonism, dyskinesia, orthostatic hypotension, anticholinergic
effects, transient asymptomatic elevations of hepatic transaminases, rash,
asthenia, fatigue and oedema.

    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.
    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. McDonnell D., Andersen S., Detke H., Watson S. 160-week interim
results from an open-label extension trial of olanzapine long-acting
injection. Data presented at Schizophrenia International Research Society
Meeting. June 21-25, 2008.
    v. 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.
    vi. 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.
    vii. 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 Neuropsychopharmacolgy Meeting. August
30-September 3, 2008.
    viii. 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
    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. 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.
    xi. 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.
    xii. 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)





For further information:

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


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