The committee reached this conclusion after analyzing the safety and efficacy data from five Phase III studies conducted in patients with treatment-resistant depression. Data from the studies demonstrated that intranasally delivered esketamine, alongside an oral antidepressant, provided statistically significant, rapid, and sustained improvement of depressive symptoms.
Spravato (esketamine) nasal spray is an investigational prescription treatment for adults with treatment-resistant depression, with a different form of drug delivery compared to current options for major depressive disorder and treatment-resistant depression.
Janssen declined our request for comment; however, according to a statement from the company, “If approved, Spravato would provide the first new mechanism of action in 30 years to treat this debilitating mental illness.”
Janssen submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) for the approval of Spravato in September 2018.
The FDA has granted breakthrough therapy designations for esketamine for treatment-resistant depression, as well as for the indication of major depressive disorder with an imminent risk for suicide.
Efficacy of intranasal drug delivery
We previously reported on Janssen’s two clinical trials for esketamine: a Phase III trial of esketamine in treatment-resistant depression, and a Phase II trial of esketamine in participants with an imminent risk for suicide.
Carla Canuso, a researcher at Janssen, explained to us the role of esketamine in the treatment of treatment-resistant depression and patients at imminent risk of suicide.
“We can engage in psychotherapies which are ultimately effective, but the treatments [for the imminently suicidal] are just safety measures that have little immediate benefit. This treatment [esketamine] was of great interest to us but also the clinical community – to have something that could work so quickly, and when I say quickly, we’re talking about hours instead of weeks,” Canuso told us.
According to Canuso, esketamine is an antimere of ketamine and a glutamate receptor modulator that can help restore synaptic connections in brain cells in people with major depressive disorder. The esketamine portion (S-Ketamine) of the ketamine molecule has a greater affinity for the N-methyl-D-aspartate (NDMA) receptor, which allows for it to be administered in lower volumes making it an appropriate choice for intranasal administration.
With intranasal drug delivery, the drug can be delivered to the central nervous system without passing through the first pass metabolism where it is processed by the liver and a portion of the dose is lost in the process, making the efficacy lower and increasing the required dosage.