In April 2025, Johnson & Johnson reported positive findings from the MDD3001 Phase 3 trial evaluating seltorexant, a selective orexin-2 receptor antagonist, as adjunctive therapy in adults with major depressive disorder (MDD) who also experience significant sleep disturbances. This pivotal study included over 600 adults who had an inadequate response to SSRIs or SNRIs and were randomized to receive either seltorexant or placebo, in combination with their existing antidepressant. The study met its primary endpoint, showing statistically significant improvements in depressive symptoms as measured by the MADRS. Notably, seltorexant also achieved meaningful improvements in key secondary sleep outcomes, including time to sleep onset and total sleep time, as assessed by both patient-reported outcomes and actigraphy. The dual benefit profile—improvement in mood and sleep—sets seltorexant apart from traditional antidepressants that often exacerbate sleep dysfunction. Safety data indicated good tolerability, with somnolence being the most common adverse event. Importantly, no significant next-day sedation or cognitive impairment was observed, underscoring seltorexant's potential as a differentiated treatment. These findings reinforce the growing recognition of sleep disturbances as a central therapeutic target in MDD. Regulatory filing is anticipated in the second half of 2025.

Citation: https://www.biospace.com/article/releases/johnson-and-johnson-announces-positive-phase-3-results-for-seltorexant-in-major-depressive-disorder-with-insomnia/

Implications: If approved, seltorexant could become the first antidepressant adjunct that directly addresses sleep dysfunction—a common and debilitating MDD symptom. Its unique mechanism may offer clinicians a dual-acting option for MDD patients with residual insomnia, a subgroup often resistant to current therapies.