FDA Finds Olanzapine Injectable "Not Approvable" for Schizophrenia
Susan Jeffrey
February 29, 2008 ? Eli Lilly & Company announced that it has received a "not-approvable" letter from the Food and Drug Administration (FDA) for its investigational long-acting injection form of the atypical antipsychotic olanzapine pamoate depot (OP depot) (Zyprexa Adhera) for the treatment and maintenance treatment of schizophrenia in adults.
"In its letter, the FDA said it needs more information to better understand the risk and underlying cause of excessive-sedation events that have been observed in about 1% of patients in clinical trials," the company said in a statement issued February 28.
These events had been the focus of a safety discussion during a meeting February 6 of the FDA's Psychopharmacologic Drugs Advisory Committee looking at this formulation, reported at that time by Medscape Psychiatry. These events, that the FDA's briefing documents noted "appear to be unique for this formulation of olanzapine," included dizziness, confusion, altered speech, or coma, occurring within 1 to 3 hours of injection. All patients recovered.
At that time, the committee ultimately agreed that there would be "circumstances under which OP depot would be acceptably safe" and effective, but with restrictions, among which was a recommended 3-hour monitoring period after injections.
However, the FDA's not-approvable letter cites another case of excessive sedation that occurred between 3 and 5 hours after the injection, outside of that previous time window, shortly before the advisory meeting.
"Lilly alerted the agency and the advisory committee about the existence of a possible new case on February 6, noting that Lilly was investigating the details of the event, including conflicting information about the time of onset," the company statement notes. "After collecting additional information, Lilly was able to confirm after the advisory committee hearing that this was a case of excessive sedation and that it began between 3 to 5 hours after the injection."
This patient also fully recovered, the company said.
"We are disappointed by the FDA's decision, and we are committed to ongoing discussions to better understand the agency's perspective regarding this recent case of excessive sedation and to define the path forward and the associated timeline," Jennifer Stotka, MD, vice president of US regulatory affairs for Eli Lilly, said in the statement.
The formulation is still under review by the European Union and other countries, including Canada and Australia, the company said.
Susan Jeffrey
February 29, 2008 ? Eli Lilly & Company announced that it has received a "not-approvable" letter from the Food and Drug Administration (FDA) for its investigational long-acting injection form of the atypical antipsychotic olanzapine pamoate depot (OP depot) (Zyprexa Adhera) for the treatment and maintenance treatment of schizophrenia in adults.
"In its letter, the FDA said it needs more information to better understand the risk and underlying cause of excessive-sedation events that have been observed in about 1% of patients in clinical trials," the company said in a statement issued February 28.
These events had been the focus of a safety discussion during a meeting February 6 of the FDA's Psychopharmacologic Drugs Advisory Committee looking at this formulation, reported at that time by Medscape Psychiatry. These events, that the FDA's briefing documents noted "appear to be unique for this formulation of olanzapine," included dizziness, confusion, altered speech, or coma, occurring within 1 to 3 hours of injection. All patients recovered.
At that time, the committee ultimately agreed that there would be "circumstances under which OP depot would be acceptably safe" and effective, but with restrictions, among which was a recommended 3-hour monitoring period after injections.
However, the FDA's not-approvable letter cites another case of excessive sedation that occurred between 3 and 5 hours after the injection, outside of that previous time window, shortly before the advisory meeting.
"Lilly alerted the agency and the advisory committee about the existence of a possible new case on February 6, noting that Lilly was investigating the details of the event, including conflicting information about the time of onset," the company statement notes. "After collecting additional information, Lilly was able to confirm after the advisory committee hearing that this was a case of excessive sedation and that it began between 3 to 5 hours after the injection."
This patient also fully recovered, the company said.
"We are disappointed by the FDA's decision, and we are committed to ongoing discussions to better understand the agency's perspective regarding this recent case of excessive sedation and to define the path forward and the associated timeline," Jennifer Stotka, MD, vice president of US regulatory affairs for Eli Lilly, said in the statement.
The formulation is still under review by the European Union and other countries, including Canada and Australia, the company said.
