Esketamine for treatment-resistant depression submitted to FDA

Janssen Pharmaceuticals, the Pharma branch of the conglomerate Johnson & Johnson, with its headquarters in New Brunswick, New Jersey, USA, announced on September 4^th, 2018, that the company submitted a New Drug Application (NDA) to the US Food and Drug Administration for esketamine nasal spray.

The requested indication is treatment-resistant depression in adults. Phase III studies for a second indication, major depressive disorder with imminent risk for suicide, are still ongoing. Esketamine had received FDA breakthrough therapy designation for treatment resistant depression in November 2013 and for major depressive disorder with imminent risk for suicide in August 2016. The company also announced that they plan to “submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication later in 2018”. Thus, it is likely that esketamine nasal spray will be available both in the US and in Europe in 2019 for the treatment of treatment-resistant depression.

The submission is based on five phase three studies, three short-term-studies, one withdrawal maintenance of effect study (in which one half of the patients were withdrawn from treatment, while the other half received continued treatment), and one long-term safety study over 52 weeks. If esketamine is approved for treatment-resistant depression, the label will most likely include treatment with a newly initiated oral antidepressant, because this was the usual treatment regime in the phase III-trials.

Esketamine acts as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Interestingly, a study published just last week in the American Journal of Psychiatry shows that the antidepressant effect of esketamine can be blocked by the opiate receptor antagonist naltrexone. This suggests an opioidergic mechanism of action of esketamine.

Janssen also announced that “esketamine nasal spray will be self-administered by patients under the supervision of health care professionals.” This is due to its abuse potential.

Esketamine for treatment-resistant depression currently receives a lot of media-attention. The “Deutsche Apotheker-Zeitung” published an article in July 2018, which is available here (in German). I gave the journal an interview, which, however, is only available for subscribers of the journal (also in German). Please leave me a note if you want to get it from me.

I will regularly post updates on the status of esketamine, which also has to undergo the AMNOG (Act on the Reform of the Market for Medicinal Products) process in Germany.