Pivotal study of seltorexant shows statistically significant and clinically meaningful improvement in depressive symptoms and sleep disturbance outcomes

Johnson & Johnson announced positive topline results from the pivotal Phase III MDD3001 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. The findings will be presented at this year’s American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which is being held from May 28-31 in Miami, Florida.

The Phase III 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 (MADRS) total score at day 43, and improved sleep disturbance outcomes, in patients who had a prior inadequate response to SSRI/SNRI 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 suffered from 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.” said Andrew Krystal, MD, Professor, Psychiatry, University of California, San Francisco Weill Institute for Neurosciences. “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.”

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 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms. Currently, no therapies are approved to treat MDD with insomnia symptoms.

Additional data presented at ASCP includes positive topline results from the placebo-controlled Phase IV TRD4005 study of Spravato (esketamine) CIII nasal spray as a monotherapy in patients with TRD (treatment-resistant depression) , which met both its primary and secondary end points. The randomized, double-blind, multicenter study showed Spravato provided rapid, statistically significant, and clinically meaningful improvement in depressive symptoms ~24 hours after the first dose and sustained through 4 weeks of treatment, as assessed by changes in MADRS total score. The safety profile of Spravato monotherapy was consistent with the registration Phase III studies of TRD in combination with an oral antidepressant, and no new safety concerns were identified.

Spravato is approved by the FDA, in combination with an oral antidepressant, for adults with TRD and depressive symptoms in adults with MDD with suicidal thoughts or behaviors. With its approval in 2019, Spravato offered the first novel mechanism of action in decades for the treatment of MDD. To date, Spravato has been administered to more than 100,000 people living with challenging-to-treat forms of depression around the world.

ABOUT MDD3001 The Phase III MDD3001 study was a randomized, double-blind, multicenter, placebo-controlled study designed to compare the efficacy and safety of oral, once daily seltorexant 20 milligrams to that of placebo, adjunctive to background SSRI/SNRI, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.