Seltorexant · program
Seltorexant (JNJ-42847922) for Major depressive disorder
Phase 3 program for adjunctive treatment of MDD with insomnia symptoms in patients with inadequate response to SSRI/SNRI. Pivotal placebo-controlled MDD3001 (NCT04533529) met all primary (MADRS change at Day 43) and secondary endpoints, announced May 2024 at ASCP. The active-comparator MDD3005 (NCT04513912, vs quetiapine XR) completed and was presented at the 2025 Psych Congress. Additional Phase 3 studies (MDD3003, NCT06559306; monotherapy MDD3011, NCT07573176) are recruiting. One Phase 3 (MDD3002, NCT04532749) was terminated at interim analysis. No publicly confirmed FDA/EMA regulatory submission or PDUFA date as of mid-2026.
Development timeline
- UpcomingConfirmatory Phase 3 MDD3003 anticipated; primary completion estimated end of 2026.
- metPivotal Phase 3 MDD3001 met all primary and secondary endpoints — significant, clinically meaningful improvement in MADRS and sleep outcomes (ASCP 2024).↗
- Phase 3 MDD3002 (NCT04532749) terminated following interim analysis on Independent Data Monitoring Committee recommendation.
- Phase 3 adjunctive MDD-with-insomnia program initiated (MDD3001, MDD3002, MDD3005).
- Phase 2b adaptive dose-finding MDD2001 (NCT03227224) completed: seltorexant 20 mg improved MADRS vs placebo at week 3 (P=.003) but the week-6 primary endpoint was not statistically significant (P=.083); larger effect in patients with greater baseline insomnia (ISI ≥15).↗
Readouts
- 2H 2026 / 2027AnticipatedTopline dataNCT06559306
Confirmatory Phase 3 MDD3003 anticipated; primary completion estimated end of 2026.
- 2024-05-29ReportedTopline datametNCT04533529
Pivotal Phase 3 MDD3001 met all primary and secondary endpoints — significant, clinically meaningful improvement in MADRS and sleep outcomes (ASCP 2024). ↗
- Date TBDReportedFull resultsNCT04513912
Phase 3 data comparing seltorexant to quetiapine XR as adjunctive therapy in MDD with insomnia symptoms presented at the 2025 Psych Congress.
Clinical trials in Major depressive disorder
NCT07573176MDD3011 (42847922MDD3011)Phase 3Recruitingn=600
Seltorexant as Monotherapy in Adults and Elderly Participants With Major Depressive Disorder
NCT06559306MDD3003 (42847922MDD3003)Phase 3Recruitingn=752
Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms
NCT04533529MDD3001 (CR108804)Phase 3Completedn=588
A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients With MDD With Insomnia Symptoms, With Open-Label Long-Term Safety Extension
metsecondarySleep disturbance outcomes (secondary)
Met all secondary endpoints, including statistically significant improvement in sleep disturbance outcomes.
metprimaryMADRS total score change from baseline to Day 43 (seltorexant 20 mg vs placebo)
Pivotal Phase 3. Met the primary endpoint — statistically significant and clinically meaningful improvement in depressive symptoms (MADRS) at Day 43 vs placebo, as adjunctive therapy to antidepressants in patients with inadequate SSRI/SNRI response. Announced at ASCP 2024.
NCT04532749MDD3002 (CR108805)Phase 3Discontinuedn=212
Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With MDD With Insomnia Symptoms (Terminated)
terminatedprimaryMADRS total score change from baseline to Day 43
Phase 3 study terminated at interim analysis on the recommendation of the Independent Data Monitoring Committee.
NCT04513912MDD3005 (CR108810)Phase 3Completedn=757
Double-Blind, Randomized Study With Quetiapine Extended Release as Comparator to Evaluate Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients With MDD With Insomnia Symptoms
pendingprimaryMADRS response rate (≥50% improvement) at Week 26, seltorexant vs quetiapine XR
Active-comparator Phase 3 vs quetiapine XR. Completed October 2023; Phase 3 data comparing seltorexant to quetiapine XR were presented at the 2025 Psych Congress. Detailed endpoint outcome not captured from a primary source here.
NCT03374475Phase 1Completedn=140
A Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Participants With Major Depressive Disorder
NCT03321526Phase 2Completedn=107
A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
NCT03227224MDD2001 (CR108281)Phase 2Completedn=287
Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants in Adult Subjects With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy
missedprimaryMADRS total score change from baseline to Week 6 (seltorexant 20 mg vs placebo) (0.083)
Phase 2b adaptive dose-finding study. Seltorexant 20 mg showed greater MADRS improvement vs placebo at week 3 (P=.003) but did NOT reach statistical significance at the week-6 primary endpoint (P=.083). Effect was larger in patients with baseline ISI ≥15. (Savitz et al., Int J Neuropsychopharmacol 2021.)
NCT02476058Phase 1Completedn=48
A Safety, Efficacy and Biomarker Study of JNJ-42847922 in Participants With Major Depressive Disorder
NCT02067299Phase 1Completedn=20
A Study to Investigate the Effect of JNJ-42847922 on Polysomnography Measures in Patients With Major Depressive Disorder With Insomnia Who Are Stably Treated With Antidepressants
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Seltorexant oral 20 mg (adjunctive, at bedtime)immediate-release oral capsule/tablet 20 mg once nightly at bedtime (qhs), adjunctive to background SSRI/SNRI antidepressant | Oral | Once nightly | t½ 2.5 h · Tmax 1 h |
Mechanism of action
Seltorexant is a potent, selective antagonist of the orexin-2 (OX2) receptor (gene HCRTR2), with roughly 100-fold (2 log) selectivity over the orexin-1 (OX1) receptor. Selective OX2R blockade reduces orexin-mediated hyperarousal — promoting sleep and potentially relieving the sleep disturbance and hyperarousal/HPA-axis components implicated in depression — without the broad sedation profile of dual orexin antagonists.
| Target | Action | Affinity |
|---|---|---|
| OX2RprimaryHCRTR2 | Antagonist | pKi 8ⓘ |
← Full Seltorexant compound page (identity, identifiers, all indications)
Sources
- Efficacy and Safety of JNJ-42847922 as Adjunctive Therapy to Antidepressants (MDD2001) — ClinicalTrials.gov
- Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study — International Journal of Neuropsychopharmacology
- clinicaltrials.gov — clinicaltrials.gov
- clinicaltrials.gov — clinicaltrials.gov
- clinicaltrials.gov — clinicaltrials.gov
- clinicaltrials.gov — clinicaltrials.gov
- J&J pivotal Phase 3 seltorexant press release (oral once-daily 20 mg, MDD with insomnia, adjunctive) — Johnson & Johnson
- Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With MDD and Insomnia Symptoms — oral, 20 mg, at bedtime, adjunctive — ClinicalTrials.gov
- Seltorexant as Adjunctive Therapy to Antidepressants in MDD With Insomnia (MDD3001) — ClinicalTrials.gov
- Seltorexant as Adjunctive Therapy to Antidepressants in MDD With Insomnia (MDD3002, terminated) — ClinicalTrials.gov
- Seltorexant as Monotherapy in Adults and Elderly Participants With MDD (MDD3011) — ClinicalTrials.gov
- Seltorexant Compared to Quetiapine XR as Adjunctive Therapy in MDD With Insomnia (MDD3005) — ClinicalTrials.gov
- The selective orexin-2 antagonist seltorexant (JNJ-42847922/MIN-202)... — oral 20 mg every evening before bedtime; half-life 2–3 h — Translational Psychiatry (PMC)