The Food and Drug Administration has issued a "not approvable" letter for a depot formulation of olanzapine.
The agency said in a letter that it is seeking to better understand the risk and underlying cause of excessive sedation events that have been observed in about 1% of patients in clinical trials," Eli Lilly & Co., manufacturer of olanzapine (Zyprexa) disclosed in late February.
Independent regulatory reviews of olanzapine long-acting injection applications are ongoing in the European Union and other countries, including Canada and Australia, Lilly said in written statement.
Despite the risk for sedation, the FDA's Psychopharmacological Drugs Advisory Committee had voted 10-0 with 1 abstention in early February that the long-acting formulation was "acceptably safe" for treating acute exacerbations and for maintenance treatment in patients with schizophrenia. The panel was not asked to vote specifically on whether to recommend approval of the drug.
The excessive sedation adverse event is unique to the new depot formulation, and occurred in 1.2% of patients and .07% of injections in clinical trials. The FDA's position was that the excess sedation is unpredictable and that the symptoms tend to be severe.
Once-daily olanzapine was first approved as an oral formula by the FDA in 1996. The depot formulation is intended for administration …