- Treatment with Johnson & Johnson's intranasal formulation of ketamine helped clear depressive symptoms in patients diagnosed with depression and who saw no improvement after taking other drugs, according to Phase 2 data published in JAMA Psychiatry on Dec. 27.
- When given esketamine on top of oral antidepressants, patients in the study experienced significant reductions in a rating scale of depressive symptoms after one week when compared to those given placebo. Results across all three doses of the drug showed a clear dose-response relationship, said J&J's pharma arm Janssen in a statement.
- Esketamine is currently in Phase 3 testing as a treatment for treatment-resistant depression and major depressive disorder with imminent risk of suicide. J&J expects to file for approval in the former indication sometime this year, and in the latter by 2020.
Previous studies have shown ketamine's potential therapeutic effect in depression, which remains a challenging condition to treat despite an array of oral antidepressants.
With esketamine, J&J has developed an intranasal formulation of ketamine that is designed to bind more effectively to a receptor called N-methyl-d-aspartate. J&J believes its candidate could help patients who no longer experience any benefit from other antidepressants, a condition known as treatment-resistant depression.
Results from the Phase 2 study showed treatment with intranasal esketamine significantly reduced total scores on the Montgomery-Asberg Depression Rating Scale (MADRS) — a gauge of depressive symptoms — when compared to placebo. Improvement was sustained for up to nine weeks in an open-label phase, even when the dosing frequency of esketamine was reduced from twice-weekly to weekly and bi-monthly.
"About one third of patients with major depressive disorder do not respond to current treatment options," said Husseini Manji, head of neuroscience at Janssen, in a Dec. 28 statement. "If approved by the FDA, esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years."
Across the double-blind and open-label phases of the study, four patients discontinued treatment with esketamine due to adverse events — compared to zero patients on placebo. Dizziness, headaches and dissociative symptoms were reported twice as frequently in the treatment arm. No deaths were reported.
The JAMA article notes, however, that the dissociative effects seen waned rapidly in most patients.
"These symptoms were dose dependent and attenuated with repeated administration. In contrast, antidepressant efficacy did not attenuate across administrations," study researchers wrote.
Esketamine is one of three neurological disease drug candidates J&J plans to file for approval between 2017 and 2021, along with an orexin-2 antagonist and an experimental treatment for schizophrenia.