A Two-Part Multicenter, Double-Blind, Randomized Placebo-Controlled Study to Evaluate Efficacy and Safety and the Maintenance of Effect of 20-(Milligram) mg Seltorexant as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients With Major Depressive Disorder With Insomnia Symptoms

The purpose of this study is to know how well seltorexant works, and also to evaluate safety and maintenance effect of seltorexant compared with placebo as an adjunctive therapy to an antidepressant in improving depressive symptoms in participants with major depressive disorder with insomnia symptoms (MDDIS) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

Start Date25 Jul 2024

Sponsor / Collaborator

Janssen Research & Development LLC

NCT05307692

/ CompletedPhase 2

A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, and Clinical Efficacy of Seltorexant (JNJ-42847922) on Behavioral and Psychological Symptoms of Dementia in Patients With Probable Alzheimer's Disease

The purpose of this study is to investigate the effect of seltorexant versus placebo on the sum of Agitation and Aggression domain scores (A plus A) of the Neuropsychiatric Inventory-Clinician rating (NPI-C) in participants with probable Alzheimer's Disease (AD) with clinically significant agitation/aggression.

Start Date19 May 2022

Sponsor / Collaborator

Janssen Research & Development LLC

NCT05236868

/ CompletedPhase 1

An Open-Label, Single-Dose Study to Assess the Absolute Oral Bioavailability and Pharmacokinetics of JNJ-42847922 (Seltorexant) Administered as Oral Tablet and an Intravenous Microdose of 14C-seltorexant in Healthy Participants

The purpose of this study is to determine the absolute bioavailability of seltorexant in healthy participants following a single oral dose of seltorexant and an intravenous (IV) infusion dose of 14C-seltorexant.

Start Date03 Feb 2022

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with Seltorexant

100 Translational Medicine associated with Seltorexant

100 Patents (Medical) associated with Seltorexant

Literatures (Medical) associated with Seltorexant

01 Mar 2025·JOURNAL OF AFFECTIVE DISORDERS

Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials

Review

Author: McIntyre, Roger S ; Kwan, Angela T H ; Rosenblat, Joshua D ; Meshkat, Shakila ; Teopiz, Kayla M ; Rhee, Taeho Greg ; Le, Gia Han ; Wong, Sabrina ; Cao, Bing ; Wang, Larry

Orexin receptor antagonists are a group of medications primarily developed to treat insomnia. Preliminary studies support their efficacy in the treatment of depression. In this systematic review, we aim to evaluate the efficacy of orexin receptor antagonists for the treatment of major depressive disorder (MDD). Electronic databases were searched from inception to February 2024 to find relevant studies. Original studies in English that evaluated efficacy of orexin receptor antagonists were included. A total of five randomized clinical trials involving 498 participants were included. Seltorexant (20 mg) significantly decreased depression scores when compared to placebo, as measured by the Hamilton Depression Rating Scale (HDRS). In patients with inadequate responses to antidepressants, seltorexant (20 mg) also showed improvement in Montgomery-Ǻsberg Depression Rating Scale (MADRS) total scores compared to placebo. However, filorexant did not exhibit a significant difference in MADRS total scores compared to placebo. A separate study on seltorexant (40 mg) for MDD patients resulted in a non-significant decrease in depressive symptoms compared to placebo, as measured by the Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR). Taken together, these findings highlight 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 their safety profile.

02 Jan 2025·EXPERT OPINION ON EMERGING DRUGS

Seltorexant for major depressive disorder

Review

Author: Cheung, William ; McIntyre, Roger S. ; Ballum, Hana ; Dri, Christine ; Choi, Hayun ; Teopiz, Kayla M. ; Valentino, Kyle ; Wong, Sabrina ; Zhang, Melanie C. ; Le, Gia Han

INTRODUCTION:

Preclinical and clinical pharmacologic evidence indicates that orexin systems are relevant to sleep-wake cycle regulation and dimensions of reward and cognition, providing the basis for hypothesizing that they may be effective as therapeutics in mental disorders. Due to the limited efficacy and tolerability profiles of existing treatments for Major Depressive Disorder (MDD), investigational compounds in novel treatment classes are needed; seltorexant, an orexin receptor antagonist, is a potential new treatment currently under investigation.

AREAS COVERED:

Mechanisms implicated in MDD, including reward and sleep, are first overviewed. Then, the safety, tolerability, and efficacy profiles of seltorexant and the wider context of orexin receptor antagonism for depression are discussed in focus. Preclinical and clinical data are also discussed. PubMed, Medline, Cochrane Library, Embase, Scopus, and Web of Science were systematically searched from inception to 10 October 2024, in accordance with PRISMA guidelines.

EXPERT OPINION:

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.

01 Sep 2023·International clinical psychopharmacology

Clinical specificity profile for novel rapid acting antidepressant drugs

Review

Author: De Ronchi, Diana ; Scala, Mauro ; Fabbri, Chiara ; Serretti, Alessandro ; Fanelli, Giuseppe

Mood disorders are recurrent/chronic diseases with variable clinical remission rates. Available antidepressants are not effective in all patients and often show a relevant response latency, with a range of adverse events, including weight gain and sexual dysfunction. Novel rapid agents were developed with the aim of overcoming at least in part these issues. Novel drugs target glutamate, gamma-aminobutyric acid, orexin, and other receptors, providing a broader range of pharmacodynamic mechanisms, that is, expected to increase the possibility of personalizing treatments on the individual clinical profile. These new drugs were developed with the aim of combining a rapid action, a tolerable profile, and higher effectiveness on specific symptoms, which were relatively poorly targeted by standard antidepressants, such as anhedonia and response to reward, suicidal ideation/behaviours, insomnia, cognitive deficits, and irritability. 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.

News (Medical) associated with Seltorexant

07 Mar 2025

·endpts.com

J&J axes Phase 3 depression program due to ‘insufficient efficacy’ shortly after Neumora’s study fail

Johnson & Johnson scrapped its Phase 3 program for aticaprant, an experimental and new type of major depressive disorder drug, following “insufficient efficacy,” the pharma giant disclosed late Thursday evening. The drugmaker was trying to bring to market a type of drug called a kappa opioid receptor (KOR) antagonist, which is meant to hit upon the reward processing and dopamine pathways. It follows a major setback from its main KOR competitor, Neumora, which flunked the first of its three Phase 3 trials in January and last week said it paused the other two studies to adjust them for a shot at better outcomes. AbbVie also has a KOR antagonist (by way of its Cerevel acquisition ) named icalcaprant. A Phase 2 study of the drug, for forms of bipolar disorder, is listed as “not yet recruiting” in the US clinical trials registry. “[T]his is a big blow to the thesis for KORAs, in our view,” Stifel analyst Paul Matteis wrote in a Thursday evening note to clients. Matteis said the decision came as a surprise since J&J was running a “very conservative” Phase 3 program with “large over-powered studies,” including an additional Phase 3 that was initiated in the fall. Two months ago, J&J doubled down in neuroscience with its proposed $14.6 billion acquisition of Intra-Cellular Therapies, which makes the marketed brain health treatment called Caplyta. A few weeks later, J&J’s global head of pharma R&D, John Reed, said the pharmaceutical and medical device conglomerate would not deprioritize its clinical-stage depression medicines, including aticaprant and seltorexant, as a result of the megadeal. “On the other hand, in retrospect,” Matteis wrote in the note, “there was JNJ’s recent decision to acquire ITCI, which may have been executed by JNJ to further their leadership in CNS under the concern that aticaprant could fail.” The setback could mark a slight dent in J&J’s future neuro prospects. The company has previously projected $1 billion to $5 billion in peak annual sales for aticaprant. In neuro, the drugmaker also markets the esketamine depression treatment called Spravato, which eclipsed $1 billion in sales for the first time last year. In a Thursday evening note, Leerink Partners analyst David Risinger said his firm had been modeling 2032 sales of aticaprant at $1.1 billion, or less than 1% of the healthcare company’s total revenue estimates for that year. Despite the setback in the Phase 3 program for the adjunctive treatment for major depressive disorder, J&J said it “will explore future development opportunities” for the late-stage asset in “other areas of high unmet need.” J&J said aticaprant was “safe and well-tolerated, and no new safety signals were identified.” The company plans to present a more complete look at the so-called VENTURA program at an undisclosed medical meeting.

Phase 3Phase 2AcquisitionCell Therapy

07 Mar 2025

·www.pharmaceutical-technology.com

J&J drops Phase III MDD programme due to lack of efficacy

J&J is now looking to trial the therapy in other indications but has not specified details. Image credit: Shutterstock / josefkubes. Johnson & Johnson (J&J) is dropping its Phase III major depressive disorder (MDD) programme for aticaprant due to ‘insufficient efficacy in the target population’. The VENTURA programme, evaluating the experimental drug as an adjunctive treatment for MDD, included five Phase III trials. The company said that despite the efficacy failure, aticaprant remained safe and well-tolerated in the programme. Full data from the VENTURA programme will be presented at a future medical meeting. J&J said it plans to “explore future development opportunities for aticaprant in other areas of high unmet need”. A statement accompanying the announcement read: “Johnson & Johnson continues to build on its leadership in neuroscience, as demonstrated by the company’s significant investments in its current pipeline and the planned acquisition of Intra-Cellular Therapies. The company remains focused on driving innovation in neuropsychiatric and neurodegenerative disorders.” There had been a lot of hope for aticaprant, with GlobalData previously touting it as the most promising pipeline product for MDD due to its novel MOA and focus on anhedonia, a hard-to-treat symptom. GlobalData analysis previously projected that aticaprant could generate global sales of approximately $670.63m in MDD by 2029 subject to approval. J&J’s high hopes for the drug were also reflected, with the company saying the therapy had the potential to make $1bn to $5bn. Reacting to J&J’s news, Phillipa Salter, neurology analyst at GlobalData said: “It is surprising to see the announcement from J&J. Aticaprant had been effective in Phase II trials and the company had only recently initiated further Phase III trials within the VENTURA programme. VENTURA-5 initiated in September 2024 and VENTURA-7 initiated in June 2024 so it is surprising that the VENTURA programme is being discontinued so soon after this. J&J were targeting adults with MDD with moderate-to-severe anhedonia which is a hard to treat symptom of severe MDD.” GlobalData is the parent company of Clinical Trials Arena . Neumora’s KOR antagonist also failed in Phase III trial Aticaprant is a kappa-type opioid receptor (KOR) antagonist that should modulate dopamine and reward processing pathways. This is the second drug with this mechanism of action (MOA) to take a hit in MDD after Neumora’s navacaprant failed to meet the the primary endpoint in the Phase III KOASTAL-1 (NCT06029426) study. Earlier this week, the US-based company announced it was halting two other studies of the drug to change the trial design of the KOASTAL-2 and KOASTAL-3 studies (NCT06058039 and NCT06058013). Neumora’s stock, listed on the Nasdaq exchange, dipped on J&J’s announcement, dropping by 13.15% from a market close of $1.52 yesterday (6 March) to a market open of $1.32 today. J&J’s stock, listed on the New York Stock Exchange (NYSE), has remained stable despite the announcement. “This news follows the recent news that Neumora Therapeutics’ navacaprant, a drug with the same mechanism of action as aticaprant, failed a Phase III trial in MDD so there was prior information that this mechanism of action may not be effective for MDD,” Salter added Last year, J&J had success in a Phase III trial of its therapy seltorexant , which helped MDD patients with insomnia, with the study meeting all its endpoints. The MDD market across the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and Canada) is poised to grow at a compound annual growth rate (CAGR) of 7.4% from $4.7bn in 2019 to $9.6bn in 2029.

Phase 3Phase 2

22 Jan 2025

·endpts.com

J&J reinforces Caplyta blockbuster projections, won't shelve neuro prospects

Johnson & Johnson made the largest splash at this year’s JP Morgan Healthcare Conference, acquiring Intra-Cellular Therapies and its neuropsychiatric drug Caplyta for $14.6 billion. On the company’s fourth-quarter earnings call Wednesday, pharma executives stood by Intra-Cellular’s projection that the drug could eclipse $5 billion in annual sales. “I know the company has guided to it being a $5 billion-plus asset; we definitely think that it will be as well,” said Jennifer Taubert, EVP and worldwide chair of the innovative medicines group. She added that J&J is also bullish on one of Intra-Cellular’s lead clinical-stage assets, ITI-1284, currently in development as a treatment for generalized anxiety disorder and Alzheimer’s disease agitation. “We see Intra-Cellular as both a near-term, as well as a long-term growth catalyst for us,” Taubert said. A major milestone for Caplyta to reach that sales figure would be snagging expanded approval as an adjunctive treatment for major depressive disorder. The biotech submitted a supplemental new drug application to the FDA in early December. Caplyta was expected to bring in more than $650 million in 2024 sales, according to Intra-Cellular. Global head of pharma R&D John Reed said that the acquisition, and Caplyta’s potential depression indication, do not mean that J&J is deprioritizing its clinical-stage depression meds. Both aticaprant and seltorexant are in Phase 3 studies as adjunctive major depressive disorder treatments. J&J previously said those drugs both have the potential to earn $1 billion to $5 billion in peak annual sales. “We see this broad portfolio, which includes, of course, Spravato, as a repertoire of different mechanisms we can bring to bear,” Reed said. Spravato has already reached blockbuster status, eclipsing $1 billion in sales in 2024. Earlier this week, it snagged an expanded label as a monotherapy for patients with treatment-resistant depression who did not respond to at least two other oral antidepressants.

AcquisitionCell TherapyPhase 3NDA

100 Deals associated with Seltorexant

External Link

KEGG	Wiki	ATC	Drug Bank
D11269	Seltorexant	-	DB14961

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 3	United States	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Argentina	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Belgium	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Bulgaria	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Canada	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Chile	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Czechia	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Denmark	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Finland	Janssen Research & Development LLC	15 Sep 2020
Depressive Disorder, Major	Phase 3	Latvia	Janssen Research & Development LLC	15 Sep 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04533529 (ASCP2024) Manual	Phase 3	Depressive Disorder, Major	588	Seltorexant	jkvoqorwso(dezgnylxdx): Difference = -2.6 (95% CI, -4.53 to -0.74), P-Value = 0.007 View more	Positive	29 May 2024
				Placebo
NCT03321526 (CTgov)	Phase 2	Depressive Disorder, Major	107	serotonin+seltorexant (Seltorexant)	ifphzgrgqy(pjxrygekki) = pgjosjzjkl qnqraelhsq (azmilftvbo, pbabcdtqgg - pxyqtvdlnl) View more	-	16 Aug 2022
				Quetiapine XR (Quetiapine XR)	ifphzgrgqy(pjxrygekki) = axbtudimti qnqraelhsq (azmilftvbo, izmtvgflwu - sfbljspnbr) View more
NCT03375203 (CTgov)	Phase 2	Sleep Initiation and Maintenance Disorders	365	Placebo	wdnyuztlct(odxvqicoqh) = feycflvmlk bqfkqlntwu (akwlqsarzx, 78.547) View more	-	23 May 2022
NCT03227224 (Pubmed \| Int J Neuropsychopharmacol)	Phase 2	Depressive Disorder, Major	287	Seltorexant 20 mg	ppkvjatgdb(jvqynthrbt): LSM difference = -4.5 (90% CI, -6.96 to -2.07)	Positive	29 Jul 2021
				Placebo

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