Long-Acting Zyprexa Faces Delay in Regulatory Process

Rochelle Nataloni

January 9, 2009 — The road to approval for the long-acting formulation of Eli Lilly’s antipsychotic drug olanzapine (Zyprexa) took a detour recently when the US Food and Drug Administration (FDA) issued a complete response letter to the company. This kind of letter explains that changes must be made before an application can be approved, with no guarantee regarding the its ultimate approvability.

While no additional clinical trials of olanzapine are required, the FDA has requested that Lilly develop a risk evaluation and mitigation strategy (REMS). This requirement generally aims to manage a known or potentially serious risk associated with a drug or biological product, and can include development of a medication guide, a patient package insert, a communication plan, elements to ensure safe use, and an implementation plan. It must also include a timetable for FDA assessment of the strategy.

Long-acting olanzapine is an injectable formulation that combines olanzapine, an atypical antipsychotic, with pamoic acid, resulting in a salt that sustains the delivery of olanzapine for up to a month. Long-acting injectables are associated with improved treatment adherence because when physicians administer a long-acting formulation, nonadherence is easily identified when a patient fails to return for a scheduled injection.

The oral formulation of olanzapine, which is indicated in the United States for short- and long-term treatment of schizophrenia, acute mixed and manic episodes of bipolar I disorder, and maintenance treatment of bipolar disorder, is typically prescribed as a once-daily tablet. The long-acting formulation is injected once every 4 weeks.

The FDA issued a not-approvable letter in February 2008 for the long-acting version of olanzapine, saying it required additional information to better understand the risk and underlying cause of excessive sedation tied to the injections in a small percentage of clinical trial patients.

Todd Durell, MD, associate medical director for US neuroscience for Lilly, said in a statement released by the drug maker that they cannot speculate on the timing of a potential decision regarding approvability, but they remain confident that, if approved, the long-acting depot formulation of olanzapine will offer an important option for treating schizophrenia.

Zyprexa is Eli Lilly’s top selling drug. It loses patent protection in 2011. The long-acting formulation of olanzapine was approved in Europe last year under the brand name Zypadhera.