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.
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.
"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, 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); a double-blind, oral olanzapine- controlled, fixed-dose study (HGKA); and six open-label studies. 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.
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; 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 per cent of injections and 1.4 per cent of patients, all of whom have recovered fully.
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 labelling, and an extensive healthcare provider training and educational programme.
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.
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.
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.