FDA Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) Endorse Esketamine

Posted by on July 24, 2019

On February 12th, 2019, Janssen Pharmaceuticals, Inc. discussed their New Drug Application (NDA) #211243 for Esketamine nasal spray during a joint meeting of the FDA’s DSaRM and PDAC. The proposed indication is for the maintenance of treatment-resistant depression (TRD).

The sponsor explained that TRD occurs when patients diagnosed with major depressive disorder (MDD) are unresponsive to at least two antidepressants. TRD is an extremely serious, life-threatening condition with increased rates of suicide, hospitalization, and impairment in daily functioning. According to the National Institute of Mental Health (NIHM), 16.2 million adults in the US have at least one MDD episode.

Esketamine works at the N-Methyl-D-aspartic acid (NMDA) neuroreceptors as an antagonist. It also enables activation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. This increases signaling of neurotrophic factors that support both a rapid onset and long-term antidepressant effects. This mechanism can help stabilize and improve TRD-related symptoms. Esketamine’s efficacy and safety was substantiated by an extensive clinical development program consisting of 19 Phase I, 4 Phase II and 5 Phase III clinical studies.

The committees answered 2 discussion questions and 3 voting questions. The most important voting question was whether the benefits of therapy outweigh the risks and if the committees supported approval of the drug. This resulted in a resounding confirmation (14 YES to 2 NO and 1 ABSTAIN).

The committee members in support explained that esketamine demonstrated sufficient evidence of effectiveness through well-characterized outcomes. They also supported the FDA’s proposed Risk Evaluation and Mitigation Strategy (REMS). Those who voted “NO” expressed their concerns regarding esketamine-related deaths, believing that the evidence supporting its efficacy was inadequate. They also raised concern about the safety of REMS.

The agency is not obligated to follow its panels’ recommendation, but normally does so.

On March 6th, FDA approved the Spravato (Esketamine) nasal spray for TRD.

ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact info@innovativescience.net

This post was authored by Sharon Christian. Sharon is a summer intern at ISS and an undergraduate student at Rutgers University.


Download ISS' Essential Guide to Preparing for a Meeting at the FDA White Oak Campus.

  • This field is for validation purposes and should be left unchanged.