In a phase 3 trial, the orexin-2 receptor agonist achieved statistically significant and clinically meaningful improvements in depressive symptoms and sleep disturbances when used as an adjunctive treatment to antidepressants.


Summary: Johnson & Johnson announced positive topline results from a phase 3 clinical trial evaluating seltorexant as an adjunctive treatment for major depressive disorder (MDD) with insomnia symptoms. The study achieved all primary and secondary endpoints, showing significant improvement in depressive symptoms and sleep disturbances. Seltorexant, a selective antagonist of the human orexin-2 receptor, was well-tolerated and safe, offering a potential new therapy for MDD patients who do not fully respond to existing antidepressants.

Key Takeaways:

  • The phase 3 trial demonstrated that seltorexant significantly improved depressive symptoms and sleep disturbances in MDD patients, meeting all primary and secondary endpoints.
  • The study focused on adults and elderly patients with MDD who experienced significant sleep disturbances and had an inadequate response to SSRIs and SNRIs.
  • Seltorexant addresses an unmet need, as no current therapies are approved specifically for treating MDD with insomnia symptoms, which affects approximately 60% of MDD patients on standard antidepressants.

Johnson & Johnson announced positive topline results from a phase 3 clinical trial evaluating the efficacy and safety of seltorexant as an adjunctive treatment to baseline antidepressants in adult and elderly patients with major depressive disorder (MDD) with insomnia symptoms. 

Seltorexant is an investigational first-in-class selective antagonist of the human orexin-2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. 

Study Achievements

The phase 3 randomized, double-blind, multicenter, placebo-controlled study achieved all primary and secondary endpoints, with seltorexant demonstrating both a statistically significant and clinically meaningful improvement in depressive symptoms, based on the Montgomery-Asberg Depression Rating Scale total score at day 43, and improved sleep disturbance outcomes in patients who had a prior inadequate response to selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs)  antidepressants alone.

These results were observed in a patient population that was assessed to be moderately-to-severely depressed despite ongoing treatment with SSRI/SNRIs and experienced significant sleep disturbance. Seltorexant was also safe and well-tolerated in the study, with similar rates of common adverse events seen in both trial arms, consistent with previous seltorexant clinical trials.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes under-treated despite being one of the most common residual symptoms,” says Andrew Krystal, MD, professor of psychiatry at the University of California, San Francisco Weill Institute for Neurosciences, in a release. “Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients.”

Presentation and Background

The findings will be presented at the American Society of Clinical Psychopharmacology’s annual meeting, which will be held from May 28 to 31 in Miami.

MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia. With insomnia, patients may have trouble falling asleep, staying asleep, or getting good-quality sleep. Approximately 60% of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms. 

Currently, no therapies are approved to treat MDD with insomnia symptoms. 

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