Quviviq (daridorexant) / Idorsia, Mochida, Syneos Health, Nxera Pharma, Simcere, Shionogi, Holling Bio-Pharma - LARVOL DELTA

Comparative effects of hypnotic agents on sleep architecture and respiratory outcomes in obstructive sleep apnea: A systematic review and network meta-analysis. (PubMed, Psychiatry Clin Neurosci) - "Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice."

Journal • Retrospective data • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Sleep, wake, and signaling: Functional profiling of orexin agonists and antagonists using newly developed orexin β-arrestin 2 and miniGαq recruitment assays. (PubMed, Eur J Pharmacol) - "These assays were successfully applied to evaluate the pharmacological profiles of both agonists and antagonists, including the endogenous ligands orexin-A and -B, the clinically approved small molecule antagonists suvorexant and daridorexant, as well as EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) and four other compounds described in literature to act at orexin receptors. The obtained receptor activation patterns and selectivity profiles were consistent with literature data, indicating the reliability and robustness of the assay systems. Overall, the newly developed assays expand the toolkit for orexin receptor research by allowing the characterization of both agonists and antagonists, thereby contributing to the functional characterization of potential new drug candidates for various pathological conditions."

Journal • CNS Disorders • Insomnia • Narcolepsy • Sleep Disorder • ARRB1

DORMI Study: Daridorexant treatment in adults with migraine and insomnia: an exploratory study of sleep and headache outcomes (ANZCTR) - P4 | N=25 | Not yet recruiting | Sponsor: Vivek Milan Keshani at Sunnybrook Hopsital, Toronto, Ontario

New P4 trial • CNS Disorders • Insomnia • Migraine • Pain • Sleep Disorder

A Study to Evaluate the Efficacy and Safety of Daridorexant in Participants With Insomnia Disorder (clinicaltrials.gov) - P3 | N=164 | Completed | Sponsor: Nxera Pharma Korea Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Insomnia • Sleep Disorder

Dose-finding Study Assessing the Efficacy, Safety, and Pharmacokinetics of Daridorexant in Subjects Aged 10 to < 18 Years With Insomnia Disorder (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Idorsia Pharmaceuticals Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Insomnia • Pediatrics • Sleep Disorder

Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking (clinicaltrials.gov) - P4 | N=44 | Not yet recruiting | Sponsor: Legacy Health System

New P4 trial • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder • Tobacco Addiction

Orexin Receptor Antagonism Improves Sleep Quality and Mitigates Lipopolysaccharide-Induced Inflammatory Responses in a Mouse Model. (PubMed, FASEB J) - "In this study, our aim was to elucidate the role of orexin in sleep and inflammatory states through the examination of a lipopolysaccharide (LPS)-induced systemic inflammatory model and the effects of daridorexant, a dual orexin receptor antagonist...These findings suggest that by reducing pro-inflammatory cytokine expression, the inhibition of orexin activity mitigates the lethargy associated with systemic inflammation, while also improving sleep quality. This study explores the potential of orexin receptor antagonists as strategic options for inflammatory pathologies and their associated sleep disorders."

Journal • Preclinical • CNS Disorders • Inflammation • Pneumonia • Sleep Disorder • CCL2 • CXCL1

Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial. (PubMed, Maturitas) - P3 | "These analyses suggest that daridorexant 50 mg provides benefit in sleep outcomes and daytime functioning in women aged 47-55 with insomnia disorder. Daridorexant 50 mg is well tolerated in this population, with no increased risk of next-morning sleepiness or somnolence."

Clinical • Journal • CNS Disorders • Fatigue • Insomnia • Sleep Disorder

Evaluating the Safety of Prescription Sleep Medications in Patients Undergoing Total Knee Arthroplasty: A Propensity Matched Analysis. (PubMed, J Am Acad Orthop Surg) - "Use of any prescription sleep medication or only standard sleep medications is associated with increased surgical complications. Additional research is needed to find medications that may be safer for routine postoperative use."

Journal • CNS Disorders • Musculoskeletal Diseases • Orthopedics • Pain • Psychiatry • Sleep Disorder

Exploratory study evaluating nightly daridorexant in patients with chronic migraine and comorbid insomnia (DORMI Study) (EHF-EHC 2025) - "Should this pilot reveal clinically meaningful improvements in sleep and headache frequency, it would warrant further investigation through a larger, randomized controlled trial."

Clinical • CNS Disorders • Insomnia • Migraine • Pain • Sleep Disorder

CELESTE: Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jan 2030 ➔ Feb 2031 | Trial primary completion date: Jan 2030 ➔ Feb 2031

HEOR • Trial completion date • Trial primary completion date • CNS Disorders • Insomnia • Sleep Disorder

PAD-DORA: Daridorexant for Alzheimer Disease Prevention (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Douglas Mental Health University Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Plasma Aβ40

Quantitative determination of suvorexant, lemborexant, and daridorexant in human plasma using a MonoTip C18 and gas chromatography-mass spectrometry. (PubMed, Forensic Toxicol) - "MonoTip C18 utilizes a reduced amount of solvent, thereby eliminating the need for evaporation-to-dryness steps. As a result, the entire procedure, encompassing SPE to GC-MS detection, can be completed within 40 min. This single protocol is applicable to all ORAs currently available in Japan and is suitable for both clinical and forensic toxicological applications."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Daridorexant to Prevent Post-cardiotomy Delirium (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: University of Rochester | Enrolling by invitation ➔ Recruiting

Enrollment status • CNS Disorders

DOREA: Dual Orexin Antagonism and Emotion and Affective Processing Study (clinicaltrials.gov) - P4 | N=62 | Recruiting | Sponsor: University of Oxford

New P4 trial

Current and novel dual orexin receptor antagonists for the treatment of insomnia: the emergence of vornorexant. (PubMed, Int J Neuropsychopharmacol) - "As an alternative target to generate novel hypnotics, the orexin system has recently gained much attention, and 3 dual orexin receptor antagonists (DORAs)-suvorexant, lemborexant, and daridorexant-were launched. Indeed, it has shown rapid sleep-promoting effects in patients with insomnia, maintaining its activity throughout the night but having a low incidence of next-day residual effects. In this review, we first provide an overview of the role of the orexin system in sleep/wake balance and then describe the profile of a newly developed DORA, vornorexant, from drug discovery to clinical results."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational Study Evaluating Four-Week Changes in Athens Insomnia Scale Among 54 Participants. (PubMed, Cureus) - "Improvements in daily function and a favorable safety profile were also observed in this participant population. These findings should be interpreted with caution, given the study's limitations, including a small sample size (n=54), short follow-up (four weeks), single-arm, and pre-post observational design."

Journal • Observational data • Real-world evidence • CNS Disorders • Depression • Insomnia • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia • Sleep Disorder

Navigating Reimbursement Challenges for Pharmacological Interventions in Celiac Disease: Lessons From Analogous Conditions (ISPOR-EU 2025) - "This research aimed to identify potential reimbursement challenges for CD drugs, draw parallels from Health Technology Assessment (HTA) reports of drugs for analogous conditions where lifestyle, non-pharmacologic therapy is a primary comparator, and propose strategies to address these challenges. A comprehensive review of published HTA reports from agencies in England, Canada, and France was conducted, focusing on drugs for obesity (Semaglutide) and insomnia (Daridorexant)... In conclusion, navigating the complex reimbursement landscape for emerging CD drugs requires a robust strategic approach. Key strategies to address identified challenges include integrating therapy with specialist multidisciplinary services, conducting comprehensive long-term clinical and economic studies (prioritizing quality of life, complication rates, and nutritional status), highlighting broader societal and economic benefits, engaging actively with patient groups and clinicians, and exploring..."

Reimbursement • US reimbursement • Celiac Disease • CNS Disorders • Genetic Disorders • Immunology • Insomnia • Obesity • Sleep Disorder

Simcere plans to produce daridorexant, a dual orexin receptor antagonist, at its plant in Hainan province, which has been inspected by the US Food and Drug Administration and the European Medicines Agency, and export it to Idorsia's global markets, the Nanjing-based company said at the CIIE, noting that it will keep exclusive rights to the drug in China. (Yicai Global)

Commercial • Insomnia

A Randomized, Open-Label, Positive-Controlled Study on the Efficacy and Safety of Daridorexant, a GABA-A Receptor Partial Agonist, in the Treatment of Patients with Recurrent Depression Complicated by Insomnia (ChiCTR) - P4 | N=80 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Wenzhou Medical University; The First Affiliated Hospital of Wenzhou Medical University

New P4 trial • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Dual orexin receptor antagonists in insomnia: Toward a new therapeutic paradigm. (PubMed, Pharmacol Biochem Behav) - "Although three dual orexin receptor antagonists (DORAs), suvorexant, lemborexant, and daridorexant, are currently available and widely used to treat insomnia, the differences in their elimination half-lives are not sufficient. However, several challenges remain to be addressed in order to fully realize the clinical potential of DORAs. This review identifies four key challenges requiring resolution to advance their optimal use in clinical practice."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Daridorexant to Prevent Post-cardiotomy Delirium (clinicaltrials.gov) - P2 | N=80 | Enrolling by invitation | Sponsor: University of Rochester

New P2 trial • CNS Disorders

Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies. (PubMed, J Psychiatr Res) - "DORAs show potential in improving sleep parameters in individuals with MDD. While their effects on depressive symptoms in this review are modest, further research is needed to assess long-term efficacy, safety, and their impact on depressive symptoms, as well as to explore potential combination therapies."

FDA event • Journal • Preclinical • Review • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis. (PubMed, Sleep Med) - "Comprehensively considering the efficacy effect size, time windows (follow-up period, age, and types of insomnia), PV, severity of imperative adverse events, we propose prioritizing the use of daridorexant 25 mg/d for insomnia characterized by difficulty maintaining sleep and insufficient sleep duration. For insomnia characterized by difficulty falling asleep, we recommend prioritizing the use of lemborexant 10 mg/day or zolpidem 10 mg/day. For overall poor sleep efficiency, we recommend using lemborexant. Drug selection should be based on the types of insomnia and drug safety. More head-to-head clinical trials are needed to confirm those findings."

Journal • Review • CNS Disorders • Insomnia • Pulmonary Disease • Sleep Disorder

PAD-DORA: Daridorexant for Alzheimer Disease Prevention (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Douglas Mental Health University Institute

New P2 trial • Alzheimer's Disease • CNS Disorders • Plasma Aβ40