Seltorexant Meets Primary, Secondary Endpoints in Phase 3 Trial for MDD, Insomnia

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Announced on May 29, 2024, data from the MDD3001 trial indicate use of seltorexant was associated with meaningful improvements in depressive symptoms and sleep disturbances.

New data from the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting suggests seltorexant met all primary and secondary endpoints in the phase 3 MDD3001 trial.

Announced by Johnson & Johnson on May 29, 2024, topline results of the trial suggest use of the investigational first-in-class selective antagonist of the human orexin-2 receptor was associated with statistically significant and meaningful improvements in depressive symptoms and sleep disturbance measures among patients with major depressive disorder (MDD) with insomnia symptoms1

“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 lead investigator Andrew Krystal, MD, professor of Psychiatry at the University of California, San Francisco Weill Institute for Neurosciences.1 “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.”

A randomized, double-blind, multicenter, placebo-controlled, the MDD3001 trial was launched to explore the safety and efficacy of seltorexant in patients who had a prior inadequate response to SSRI/SNRI antidepressants alone. According to the May 29, 2024, announcement from Johnson & Johnson, use of the agent was associated with 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.1

Safety analyses of the trial detailed a safety profile consistent with previous clinical trials. According to investigators, the agent was safe and well-tolerated in the study, with similar rates of common adverse events seen in both trial arms.1

“For nearly seven decades, Johnson & Johnson has delivered transformational treatments and solutions for people living with serious mental illness, and we are proud to present these data from our marketed and late-stage neuropsychiatry portfolios at ASCP,” said Bill Martin, PhD, global therapeutic area head of Neuroscience at Johnson & Johnson.1

At the Associated Professional Sleep Societies’ 38th Annual Meeting, SLEEP 2024, data from a randomized controlled trial provided further insight into the effects of seltorexant among patients with MDD. a randomized, double-blind, placebo- and positive-controlled 4-way crossover study assesses the effects of bedtime administration of seltorexant on morning driving performance in 37 adults with MDD taking an SSRI/SNRI and 26 elderly participants, including 19 with MDD and 7 healthy controls.2

Results of the trial suggested there were no clinically relevant changes in driving performance in adults and elderly patients with MDD with mean differences between seltorexant and placebo following seltorexant 20-mg and 40-mg on days 2 and 9 failing to recharge the prespecified 2.4 cm threshold. Of note, driving performance was measured as standard deviation of lateral position.2


  1. Johnson & Johnson. Johnson & Johnson pivotal study of SELTOREXANT shows statistically significant and clinically meaningful improvement in depressive symptoms and sleep disturbance outcomes. May 29, 2024. Accessed May 30, 2024.
  2. Devineni D, Li L, Zhou X, et al.On-road Driving Performance the Morning After Bedtime Seltorexant in Major Depressive Disorder and Healthy Elderly. Abstract presented at Associated Professional Sleep Societies’ 38th Annual Meeting, SLEEP 2024. Houston, TX. June 1-5, 2024.