Janssen Pharma files NDA at FDA for esketamine nasal spray to treat treatment-resistant depression.

The Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) announced the submission of a New Drug Application (NDA) to the FDA for esketamine nasal spray. Janssen is seeking FDA approval of esketamine for treatment-resistant depression in adults. Esketamine is an investigational, rapidly acting antidepressant that works differently than currently available therapies for major depressive disorder. Through glutamate receptor modulation, esketamine is thought to help restore connections between brain cells in people with treatment-resistant depression.

"Of the nearly 300 million people who suffer from major depressive disorder worldwide, about one-third do not respond to currently available treatments. This represents a major unmet public health need," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are committed to working with the FDA to bring this new treatment option to U.S. patients with treatment-resistant depression and to the medical community."

The NDA is based on five pivotal Phase III studies of esketamine nasal spray in patients with treatment-resistant depression: three short-term studies, one withdrawal maintenance of effect study, and one long-term safety study. Data from these studies demonstrate that treatment with esketamine nasal spray plus a newly initiated oral antidepressant compared to placebo nasal spray plus a newly initiated antidepressant was associated with rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression. The long-term safety study showed that the esketamine doses studied were generally tolerated, with no new safety signals with dosing up to 52 weeks, compared to data from the short-term esketamine studies. The short-term esketamine Phase III study in adults with treatment-resistant depression included a newly initiated oral antidepressant in both the control and placebo groups.The U.S. FDA granted Breakthrough Therapy Designations for esketamine nasal spray for treatment-resistant depression and for a second indication, major depressive disorder with imminent risk for suicide. Janssen is currently conducting Phase III clinical studies for the second indication. Janssen plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication later in 2018.

Comment: Summary of trials: Of the first two short-term Phase III trials to report, only one met the primary efficacy endpoint, while the other showed a �meaningful� improvement, though not statistically significant, in patients with treatment-resistant depression. That study was the first of its kind targeted to patients 65 and older.Two long-term Phase III studies are also included in the submission to the FDA including one that showed a delayed time to relapse in patients taking esketamine plus an oral antidepressant versus those taking a placebo nasal spray plus an oral antidepressant, as well as a trial that provided evidence of safety for up to one year.