On Tuesday, a U.S. Food and Drug Administration advisory panel overwhelmingly supported approval of the nasal spray treatment.
Molecule of esketamine, used to treat major depressive disorder.
Johnson & Johnson’s esketamine nasal spray to treat major depression is one step closer to regulatory approval in the United States.
On Tuesday, a U.S. Food and Drug Administration (FDA) advisory panel overwhelmingly supported approval of the nasal spray treatment. The FDA’s Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee met in a joint committee to review the clinical data of the medication. After the testimony, the panel voted 14-2, with one abstention, in favor of the efficacy of the treatment and that the benefits outweigh the risks, according to Seeking Alpha, which was the first outlet to report the results. Also, the panel’s vote was 15 - 2 in favor of the safety profile of the esketamine treatment.
Esketamine nasal spray is being developed by Janssen Research & Development, a division of Johnson & Johnson. Janssen’s esketamine nasal spray is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, which is also known as a glutamate receptor modulator. Janssen believes the treatment works by restoring synaptic connections in brain cells in individuals with major depressive disorder. If the FDA gives the green light to the esketamine spray, it will be the first new approach for treating refractory major depressive disorder in nearly 50 years.
Before the advisory panel met, there were some concerns about the potential approval of the treatment, particularly over its potential for abuse. BioSpace reported last week ahead of the advisory panel meeting, FDA staff noted that esketamine, which is related to the well-known party drug ketamine, appears to induce a dreamlike sensation in some users. However, FDA staff said that ketamine abuse is “relatively uncommon in the general population.” In addition to the potential for the dreamlike sensation, there were also some concerns that the treatment could increase blood pressure in some patients.
Janssen filed its New Drug Application based on the results of five Phase III trials. In May, the company unveiled Phase III results from two clinical studies. Data from those studies showed a combination of the flexibly dosed esketamine nasal spray and a newly initiated oral antidepressant demonstrated a “statistically significant, clinically meaningful rapid reduction of depressive symptoms as compared to placebo.” The first Phase III study included adults with treatment-resistant depression, which was defined as “patients who had not responded to two or more currently available antidepressants of adequate dose and duration in the current episode of depression.” Data from another trial showed that about 69 percent of the study group responded to the drug after 4 weeks compared to 52 percent in the intranasal placebo group. While those trials were hailed a success, one Phase III trial failed to hit the mark. The results of that trial, released in September 2018, revealed the esketamine nasal spray failed to show statistical significance for the primary endpoint, change in a depression severity rating scale score from baseline to four weeks, for the 84 mg dose plus an oral antidepressant compared to oral antidepressant and placebo.
With the advisory panel out of the way, Janssen is now eying a March 4 PDUFA data. Esketamine received Breakthrough Therapy Designations from the FDA in November 2013 for treatment-resistant depression. It received the same designation in August 2016 for the indication of major depressive disorder with imminent risk for suicide.
