The therapy, when combined with oral antidepressant, reported a 70% reduction in relapse risk for depression versus standard-of-care.
Ella Daly, MD
New results from a couple of long-term phase 3 clinical trials report the investigational compound esketamine nasal spray is efficacious and safe in delaying relapse time for patients with treatment-resistant depression.
The research, from Janssen Pharmaceutical Companies of Johnson & Johnson, assessed esketamine nasal spray plus oral antidepressant versus placebo plus oral antidepressant in delaying time to relapse of depression symptoms in patients who suffer from treatment-resistant depression. It follows 2 studies presented at the American Psychiatric Assocation's Annual Meeting in New York, NY, las week, which showed the drug's efficacy in short-term duration.
The findings are significant both for the drug — which is being considered for US Food and Drug Administration (FDA) — and for a worldwide patient population of more than 300 million.
The therapy is a glutamate receptor modulator, considered capable of restoring synaptic connections in the brains of patients with depression. Its novel mechanism of action gives it distinction among a limited market of available or effective antidepressant treatments for this patient population. According to Janssen, the common “full antidepressant effect” provides relief after 3-4 weeks.
The first trial, a randomized, double-blind, multi-center study of 705 adult patients directly enrolled or transferred from previous esketamine phase 3 trials, compared 56 or 84 mg nasal spray plus oral antidepressant versus a placebo-antidepressant regimen in intermittent dosing over 16 weeks.
Researchers gauged stable remission in patients as a Montgomery-Asberg Depression Rating Scale (MADRS) total score of 12 or less in at least 3 of 4 weekly assessments conducted during weeks 12-16. Relapse criteria was set at MADRS scores of at least 22 for 2 consecutive weeks, or hospitalization for worsening depression.
Patients who were given esketamine combination therapy reported significant delayed relapse versus placebo-plus-antidepressant. Among stable patients in remission 24 (26.7%) patients given esketamine reported a relapse event during their maintenance phase, versus 39 (45.3%) of patients given placebo (P = 0.003).
Time to relapse among patients with a stable response that didn’t include remission was more frequent in the placebo group (34; 57.6%) than the esketamine group (16; 25.8%). Based on Cox proportional hazards, researchers concluded the esketamine-plus-antidepressant regimen reduced relapse risk by 70% (P < 0.001).
The second study, an open-label trial that assessed 52-week safety and efficacy of the nasal spray in patients, showed esketamine was tolerable with an oral antidepressant, and no new safety signals after repeated long-term dosing. The reported safety profile was similar to that observed in previous short-term phase 2 and 3 trials in patients with treatment-resistant depression, and a low drop-out rate (6.8% from baseline to week 4; 3.8% in the following weeks) attributed to adverse events.
The promising study results compliment a portfolio of 5 total pivotal phase 3 studies of esketamine nasal spray in patients with treatment-resistant depression, which will comprise Janssen’s submissions to regulatory agencies for approval. According to the company, an approval from the FDA will make esketamine one of the first new therapies for refractory major depressive disorder in the last 50 years.
Currently, 6 million patients in the US suffer from treatment-resistant depression, which is commonly associated with greater rates of relapse. Ella Daly, MD, director of Clinical Research, Janssen R&D, told MD Magazine the condition brings on a worse quality of life for patients, who are burdened with more costs of care and limited benefit from medicine.
“Patients with treatment resistant depression are also at risk for hospitalization and have a higher risk of suicide because of their illness,” Daly said. “This great unmet need points to the importance of continued research in depression with discovery and development of new treatment options.”
Daly expressed Janssen's intentions to submit the therapy to the FDA and European regulatory agencies for marketing consideration later this year.