seltorexant (MIN-202) / Minerva Neurosciences, J&J - LARVOL DELTA

Activation of orexin receptor 2 plays anxiolytic effect in male mice. (PubMed, Brain Res) - "In this study, by using behavioral test, stereotaxic surgery and microinjection, virus-mediated knockdown of OX2R and pharmacological method, we found that: (1) Intraperitoneal injection of OX2R antagonist Seltorexant induced increased baseline anxiety-like behaviors in male mice...(3) Intraperitoneal injection of YNT-185 alleviated morphine withdrawal-induced anxiety-like behaviors in male mice. (4) Microinjection of YNT-185 into the VTA played anxiolytic effect in male mice. (5) Virus-mediated OX2R knockdown in the VTA induced anxiety-like behaviors in male mice."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry

Seltorexant for major depressive disorder. (PubMed, Expert Opin Emerg Drugs) - "Early clinical evidence suggests that seltorexant is effective in treating MDD, both in individuals diagnosed with insomnia and those not, although greater antidepressant effects are observed in individuals with severe sleep disturbance. Results from large phase III clinical trials are needed to confirm efficacy and safety."

Journal • Review • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Sleep Disorder

Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial. (PubMed, Mol Psychiatry) - P1 | "These biomarker data suggest mechanistic hypotheses that may account for the apparent curvilinear dose-response relationship of seltorexant. Trial Registration: ClinicalTrials.gov, NCT03374475."

Clinical • Journal • Monotherapy • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials. (PubMed, J Affect Disord) - "However, filorexant did not exhibit a significant difference in MADRS total scores compared to placebo. Taken together, the potential of orexin receptor antagonists, particularly seltorexant, as a novel avenue for managing depressive symptoms in MDD. Further research is warranted to better understand their role in depression treatment and safety profile."

Clinical • Journal • Review • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Phase 3 study of adjunctive seltorexant treatment in adults with major depressive disorder with insomnia symptoms (ECNP 2024) - P3 | "Seltorexant demonstrated statistically significant and clinically meaningful antidepressant effects, beyond improvement of insomnia symptoms, in the global efficacy analysis set of participants with MDD with IS experiencing an inadequate response to SSRI/SNRI. These Results were consistent in the EU efficacy analysis set. The safety and tolerability profile of seltorexant was similar to that of placebo."

Clinical • P3 data • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms (clinicaltrials.gov) - P3 | N=752 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2027 ➔ Nov 2027

Trial completion date • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Phase 3 Study of Adjunctive Treatment With Seltorexant in Adult and Elderly Participants With Major Depressive Disorder and Insomnia Symptoms (clinicaltrials.gov) - P3 | N=752 | Recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Depression clinical trials worldwide: a systematic analysis of the ICTRP and comparison with ClinicalTrials.gov. (PubMed, Transl Psychiatry) - "The top four most studied drugs, ketamine, sertraline, duloxetine, and fluoxetine, were consistent in both groups, but ClinicalTrials.gov had more trials for each drug compared to the non-ClinicalTrials.gov group. Additionally, 26 investigational antidepressive agents targeting 16 different drug targets were identified, with buprenorphine (opioid agonist), saredutant (NK2 antagonist), and seltorexant (OX2 antagonist) being the most frequently studied. This analysis addresses 40 approved drugs for depression treatment including new drug classes like GABA modulators and NMDA antagonists that are offering new prospects for treating MDD, including drug-resistant depression and postpartum depression subtypes."

Clinical • Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: Janssen Research & Development, LLC | Trial completion date: Mar 2025 ➔ Apr 2024 | Active, not recruiting ➔ Terminated; Following discussion on pediatric strategy with HAs, it was determined that we have sufficient data to inform next steps for the seltorexant pediatric program.

Monotherapy • Trial completion date • Trial termination • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant (clinicaltrials.gov) - P3 | N=588 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Seltorexant, Adjunctive to Antidepressants, in Adults with MDD with Insomnia Symptoms: Results of a Double-Blind, Randomized, Placebo-Controlled Study (ASCP 2024) - P3 | "Seltorexant showed statistically significant and clinically meaningful antidepressant effects, beyond improvement of insomnia symptoms, in patients with MDD with IS who had experienced inadequate response to SSRI/SNRI. Seltorexant demonstrated a safety profile similar to placebo. Learning Objectives 1."

Clinical • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Adjunctive Treatment with Seltorexant Improved Patient-Reported Depressive Symptoms, Insomnia Symptoms, and Overall Health in MDD with Insomnia (ASCP 2024) - P3 | "From the patient’s perspective, adjunctive treatment with seltorexant improved depressive symptoms, insomnia symptoms, and HRQoL, compared to placebo, in adults with MDDIS and an inadequate response to SSRI/SNRI. Learning Objectives 1. Describe secondary and exploratory endpoints of a phase 3 study investigating the efficacy and safety of seltorexant, adjunctive to background SSRI/SNRI antidepressant, in patients with major depressive disorder with insomnia symptoms."

Clinical • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting | N=52 ➔ 31 | Trial primary completion date: Feb 2025 ➔ Apr 2024

Enrollment change • Enrollment closed • Monotherapy • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis. (PubMed, Noro Psikiyatr Ars) - "Search words were (depression OR mood disorder OR affective disorder) AND (orexin OR orx OR hypocretin OR orx1 OR orx2 OR orexin receptor antagonist OR almorexant OR suvorexant OR lemborexant OR daridorexant OR seltorexant OR vornorexant OR filorexant). Considering the physiological effects of orexin on behaviors, ORAs may be promising new treatment modalities in the treatment of many psychiatric disorders other than insomnia. However, these results are preliminary and further studies with different ORAs at different doses and with different samples are needed."

Journal • Retrospective data • Review • CNS Disorders • Depression • Insomnia • Mental Retardation • Mood Disorders • Psychiatry • Sleep Disorder

A Study of Seltorexant in Participants With Probable Alzheimer's Disease (clinicaltrials.gov) - P2 | N=70 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Dementia

Pyrazole derivatives as selective orexin-2 receptor antagonists (2-SORA): synthesis, structure-activity-relationship, and sleep-promoting properties in rats. (PubMed, RSC Med Chem) - "Selective orexin 2 receptor antagonists (2-SORA) such as seltorexant (15) are in clinical development for the treatment of insomnia and other conditions such as depression...Compounds were assessed for their brain-penetrating potential in in vivo experiments to select the most promising compounds for our in vivo sleep model. Our lead optimization efforts led to the discovery of the potent, brain penetrating and orally active, 2-SORA (N-(1-(2-(5-methoxy-1H-pyrrolo[3,2-b]pyridin-3-yl)ethyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide) 43 with efficacy in a sleep model in rats comparable to 15."

Journal • Preclinical • CNS Disorders • Depression • Insomnia • Psychiatry • Sleep Disorder

A Study of Seltorexant Compared to Quetiapine XR as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy (clinicaltrials.gov) - P3 | N=757 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

A Study to Determine the Abuse Potential of Seltorexant Compared to Suvorexant and Zolpidem (clinicaltrials.gov) - P1 | N=127 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed

Trial completion

Clinical specificity profile for novel rapid acting antidepressant drugs. (PubMed, Int Clin Psychopharmacol) - "This review discusses the clinical specificity profile of new antidepressants, namely 4-chlorokynurenine (AV-101), dextromethorphan-bupropion, pregn-4-en-20-yn-3-one (PH-10), pimavanserin, PRAX-114, psilocybin, esmethadone (REL-1017/dextromethadone), seltorexant (JNJ-42847922/MIN-202), and zuranolone (SAGE-217). The main aim is to provide an overview of the efficacy/tolerability of these compounds in patients with mood disorders having different symptom/comorbidity patterns, to help clinicians in the optimization of the risk/benefit ratio when prescribing these drugs."

Journal • CNS Disorders • Cognitive Disorders • Insomnia • Mood Disorders • Psychiatry • Sexual Disorders • Sleep Disorder • Suicidal Ideation

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Participants With Major Depressive Disorder With Insomnia Symptoms Who Have Responded Inadequately to Antidepressant and Long-term Safety Extension Treatment With Seltorexant (clinicaltrials.gov) - P3 | N=588 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2023 ➔ Apr 2024

Enrollment closed • Trial completion date • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

A Study of Seltorexant in Participants With Probable Alzheimer's Disease (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Apr 2023 ➔ Oct 2023

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

A Study of Seltorexant as Adjunctive Therapy to Antidepressants in Adolescents With Major Depressive Disorder Who Have an Inadequate Response to Selective Serotonin Reuptake Inhibitor (SSRI) and Psychotherapy (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Nov 2023 ➔ Mar 2025 | Trial primary completion date: May 2023 ➔ Feb 2025

Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Characteristics of Seltorexant-Innovative Agent Targeting Orexin System for the Treatment of Depression and Anxiety. (PubMed, Molecules) - "Pre-clinical and clinical studies are also described, including side effects. There is evidence that the use of seltorexant is considered safe, with no clear or major clinically significant side effects, which makes it a promising candidate for the treatment of depression and anxiety disorders."

Journal • Review • CNS Disorders • Depression • Genetic Disorders • Insomnia • Mood Disorders • Obesity • Psychiatry • Sleep Disorder

A Study to Determine the Abuse Potential of Seltorexant Compared to Suvorexant and Zolpidem (clinicaltrials.gov) - P1 | N=150 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Mar 2023 ➔ Jun 2023 | Trial primary completion date: Mar 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date

A Study of Oral Seltorexant as an add-on Medication to an Antidepressant on On-road Driving Performance in Participants With Major Depressive Disorder (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: Janssen Research & Development, LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry