Zypadhera(TM) Receives Positive Opinion from the European Committee for Medicinal Products for Human Use (CHMP) for Maintenance
INDIANAPOLIS, Sep. 26, 2008 (Canada NewsWire via COMTEX News Network) — 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 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 (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 olanzapine LAI Post-Injection Syndrome. (v) Additionally, the trials showed that olanzapine long-acting injection (LAI) 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)
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.
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.
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 >/= 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.
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
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.