Esketamine nasal spray effective for treatment-resistant depression
Adjunctive treatment with intranasal esketamine demonstrated long-term safety and delayed time to relapse in patients with treatment-resistant depression, according to results from two long-term phase 3 clinical studies presented at the American Society of Clinical Psychopharmacology annual meeting.
These findings follow other phase 3 data presented at the American Psychiatric Association annual meeting supporting esketamine nasal spray for treatment-resistant depression.
“Depression is the number one cause of disability worldwide. Unfortunately, about one-third of patients with major depressive disorder do not respond to multiple antidepressants and are considered to have treatment-resistant depression,” Jaskaran Singh, MD, senior director of clinical research at Janssen Pharmaceuticals, told Healio Psychiatry.
“This great unmet need points to the importance of continued research in depression with discovery and development of new treatment options,” he continued. “Janssen has pioneered the development of many groundbreaking mental health products for more than 50 years; esketamine nasal spray is the latest example of our innovative approach to research in neuroscience and psychiatry.”
Relapse prevention study
In a phase 3, randomized, double-blind, multicenter study, researchers examined relapse prevention in adults with treatment-resistant depression. The investigators randomly assigned 705 adults enrolled from other esketamine phase 3 studies — those who were in stable remission and those who had only stable response — to receive esketamine nasal spray (56 mg or 84 mg) plus an oral antidepressant or an oral antidepressant plus placebo nasal spray with repeated, intermittent dosing over 16 weeks.
Time to relapse among patients who were in stable remission after 16 weeks of treatment with intranasal esketamine plus an oral antidepressant was the primary efficacy endpoint and time to relapse among those with stable response but without remission was the secondary endpoint.
Overall, esketamine nasal spray along with an oral antidepressant with repeated, intermittent long-term dosing demonstrated safety and tolerability, according to a press release. Continuous treatment with esketamine nasal spray plus an oral antidepressant for more than 16 weeks showed superiority to treatment with standard of care plus placebo in delaying time to symptom relapse.
In total, 26.7% of patients with stable remission who received esketamine plus an oral antidepressant and 45.3% of those who received oral antidepressant plus placebo experienced a relapse event (P = .003) during the maintenance phase, according to the release. Among patients with stable response only, 25.8% of patients in the esketamine nasal spray group and 57.6% of those in the placebo group relapsed. The results indicated that that patients treated with esketamine plus an oral antidepressant had a 70% reduced risk for relapse (HR = 0.3; 95% CI, 0.16-0.55).
The most common treatment-emergent adverse events that occurred in the esketamine group included metallic taste, vertigo, dissociation, drowsiness, dizziness, headache, nausea, vision blurred and oral hypoaesthesia. Adverse events were usually brief and resolved on the day of dosing, per the release.
Long-term safety study
In this phase 3, open-label, safety study, 802 adults with treatment-resistant depression received intranasal esketamine (28 mg, 56 mg or 84 mg) plus an oral antidepressant with repeated, intermittent dosing for up to 1 year to determine its long-term safety and efficacy.
Overall, treatment with intranasal esketamine and an oral antidepressant was tolerable and did not yield any new safety signals after repeated long-term dosing, according to the press release. At day 28 (endpoint), the response rate was 78.4% and the remission rate was 47.2%, according to the release. After 52 weeks, 76.5% of participants who responded to treatment and continued to the optimization/maintenance phase were responders and 58.2% were remitters.
These findings also suggested that this treatment appeared to sustain improvement in depressive symptoms for up to 1 year; however, the open-label design did not allow for formal evaluation of its efficacy. The most common adverse events relating to treatment with esketamine nasal spray and an oral antidepressant included dizziness, dissociation, nausea, headache, drowsiness, metallic taste and oral hypoaesthesia, vertigo, vomiting and viral upper respiratory tract infection. In total, five serious treatment-emergent adverse events were esketamine nasal spray-related, according to the release.
Like the safety profile of esketamine observed in previously completed short-term phase 2 and phase 3 studies for treatment-resistant depression, the study had a low drop-out rate due to adverse events — 6.8% in the initial 4-week induction phase and 3.8% in the 48- week optimization/maintenance phase, according to the release.
“The results of these studies are exciting for patients and clinicians,” Ella Daly, MD, director of clinical research at Janssen Research & Development, U.S., told Healio Psychiatry. “The recently completed relapse prevention study demonstrates that esketamine may be beneficial in terms of delaying time to relapse for patients with treatment-resistant depression, and the long-term, open-label, safety study demonstrates the safety and tolerability of repeated intermittent dosing with esketamine nasal spray for up to 1 year in this patient population. These findings provide hope for the 300 million people worldwide living with treatment-resistant depression.” – by Savannah Demko
Daly E, et al. Abstract W68.
Wajs E, et al. Abstract T67. Presented at: American Society of Clinical Psychopharmacology Annual Meeting; May 29-June 1, 2018; Miami Beach, Florida.
Disclosures: Singh and Daly are both employees of Janssen.