The US Food and Drug Administration says it needs more information on the excessive sedation effects seen in some patients taking Eli Lilly’s long-acting schizophrenia drug Zyprexa before it will consider the drug’s approval.

Zyprexa LAI is an injectable form of the olanzapine that provides extended delivery of up to four weeks, thereby potentially improving treatment compliance and better outcomes.
However, in clinical trials of the long-acting version, 24 out of 1,915 patients who received the jab suffered excessive sedation, which typically lasted around one to three hours and even induced coma in two cases. All patients suffering these side effects fully recovered within 72 hours.

The FDA’s move goes against the recommendation of an advisory panel, which, earlier this month, voted that with appropriate labeling to describe these events the injectable drug is effective for the acute and long-term treatment of schizophrenia and is “acceptably safe”.

But in its letter to Lilly, the Agency explained it needs to better understand the risk and underlying cause of such events, particularly as a further suspected case of excessive sedation that occurred just before the advisory panel met was subsequently confirmed.

Delay a ‘disappointment’
The delay to Zyprexa’s approval will obviously come as a disappointment to Lilly, which said it is currently in ongoing discussions with the regulators to determine “the path forward and associated timeline”.

But Jennifer Stotka, vice president of US Regulatory Affairs at the firm, re-iterated the group’s confidence in the drug, saying: "Given the chronic and severe nature of schizophrenia, persistent challenges with adherence, and the limited number of approved depot formulations, we continue to believe that, if approved, Zyprexa LAI would provide a valuable treatment option for patients suffering from schizophrenia."

Zyprexa first hit the market in 1996 and is currently indicated in the US for the short- and long-term treatment of schizophrenia, acute mixed and manic episodes of bipolar disorder, and maintenance treatment of bipolar disorder. The drug generated sales of $1.27 billion in the fourth quarter of 2007.