Novel Nasal Spray Improves Symptoms in Patients with Treatment-Resistant Depression

Data from two phase 3 studies showed that esketamine nasal spray demonstrated improvements in depressive symptoms for patients who did not respond to other antidepressant treatments.

A new nasal spray therapy showed rapid improvement in patients with treatment-resistant depression, according to recent data from two phase 3 clinical trials.

The Janssen Pharmaceutical Companies of Johnson & Johnson announced positive findings from their latest data on the use of esketamine nasal spray to improve depressive symptoms in patients who had not responded to 2 or more currently available antidepressants. Esketamine nasal spray, a non-competitive N-methyl-D-aspartate receptor agonist, is an investigational compound thought to help restore synaptic connections in brain cells in patients with major depressive disorder.

According to the press release, the results demonstrated the potential of the treatment to address a significant unmet need for more than 30% of individuals with treatment-resistant major depressive disorder.

In the first study, flexibly-dosed esketamine nasal spray plus a newly initiated oral antidepressant demonstrated a statistically significant, clinically meaningful, rapid reduction of depressive symptoms compared with a placebo plus an oral antidepressant.

Treatment-resistant was defined as patients who had not responded to 2 or more currently available antidepressants of adequate dose and duration in the current episode of depression.

The study enrolled adults with moderate-to-severe, non-psychotic, recurrent or persistent depression, and a history of treatment resistance. Those with treatment-resistant depression were randomized to receive flexibly-dosed esketamine nasal spray (56 or 84 mg twice weekly).

In the second study, esketamine was evaluated in patients aged 65 years and older with treatment-resistant depression. To improve tolerability, patients were given a lower starting dose (28 mg) of esketamine nasal spray (flexibly dosed as 28 mg, 56 mg, or 84 mg) plus a newly initiated oral antidepressant or placebo nasal spray, plus a newly initiated oral antidepressant.

However, the study narrowly missed statistical significance for its primary efficacy endpoint.

“The positive phase 3 results for esketamine nasal spray in adults with treatment-resistant depression are exciting, particularly as they mark the first time an antidepressant has achieved superiority versus an active comparator in any clinical trial for major depressive disorder,” Husseini K. Manji, MD, global head of Janssen Research & Development’s neuroscience therapeutic area, said in the press release.

“What makes this even more significant is that the response was rapid and this milestone was achieved in patients deemed to be treatment-resistant. We are also pleased with the clinically meaningful outcomes for esketamine nasal spray in elderly patients, a population that often has greater disability and lower response rates.”

Reference

New Phase 3 Data Show Esketamine Nasal Spray Demonstrated Rapid Improvements in Depressive Symptoms in Patients with Treatment-Resistant Depression [news release]. Janssen’s website. http://www.janssen.com/new-phase-3-data-show-esketamine-nasal-spray-demonstrated-rapid-improvements-depressive-symptoms. Accessed May 14, 2018.