Antidepressant Long-Term Efficacy Pre-Approval Will Be Voted On By Cmte.

FDA will ask whether it is reasonable to require both acute and long-term efficacy data in applications for antidepressants and other chronic psychiatric drugs at its Psychopharmacologic Drugs Advisory Committee meeting on Oct. 25.

The agency will request a vote on the question: "Is it a reasonable expectation that a sponsor would have accumulated data from both acute and longer-term efficacy trails at the time of filing of an application for a drug for the treatment of" major depressive disorder?

FDA will then ask whether it is reasonable to expect that "the sponsor must have demonstrated both acute and longer-term efficacy for MDD?"

The initial questions from FDA are specific to major depressive disorder, but later in the meeting the agency will ask whether the committee's answers to the questions also apply to drugs for other chronic psychiatric illnesses.

[Editor's Note: To ¹ watch a webcast or order a video/DVD of this meeting, visit FDAAdvisoryCommittee.com.]

Over the past six months, FDA has "been taking the position that, for chronic psychiatric illnesses, it is necessary to have both acute and longer-term efficacy data to support even an initial efficacy claim for a drug," FDA Division of Psychiatry Products Director Thomas Laughren explained in a ² memorandum.

FDA added that "this proposed policy has been met with considerable resistance and questions, and for this reason, we thought it would be useful to bring this general issue to the committee for discussion."

If a drug fails to show efficacy in acute or maintenance therapy, FDA asks the committee whether it could approve one indication and include information about failed efficacy in the other indication.

"If the acute studies support an acute claim, but the longer-term trial fails to demonstrate an effect, could the drug be approved for short-term use, with a mention of negative longer-term findings in the label?"

Drugs could also be approved for longer-term use only, if acute trials fail, FDA suggested, with language in labeling about negative findings in acute disease.

FDA cites Lamictal as a drug that was approved for a maintenance indication in bipolar I disorder without evidence of acute efficacy; however, Lamictal labeling did not mention the negative findings in acute disease.

The committee will be asked to discuss "at what point in a development program for a drug for MDD should this new requirement for longer-term data at the time of filing of an application be implemented."

"We feel that the phase of development should be taken into consideration in the implementation of the new policy, because the consequences of implementing such a policy late in the development could be viewed as detrimental to the public health if the impact of a last minute policy shift is the delay in introduction of a promising drug, or even the termination of a program."

Design questions for long-term trials will also be discussed at the committee meeting.

The agency will ask about the minimum period of time that patients with MDD should remain in responder status before being randomized in a withdrawal (relapse prevention) study.

FDA has "suggested six months as a duration that is clinically relevant and consistent with treatment guidelines regarding the recommended duration of therapy after response to acute treatment for many chronic psychiatric conditions, including MDD."

In briefing materials for the committee, Vanda Pharmaceuticals asserted that the stabilization period for patient response should be closer to one month for antipsychotic agents. [Editor's note: For full coverage of Vanda Pharmaceuticals' comments, go to ³ "The Pink Sheet"DAILY.com .]

The committee will also be asked to consider whether it is reasonable for patients to be considered responders in an open run-in phase of a long-term trial if they have minor and temporary excursions above criterion scores, or minor dosage adjustments.

Similarly, the committee will weigh in on whether minor and temporary excursions above criterion scores or slight dose adjustments are acceptable in the randomized phase "without considering such patients to have relapsed."