Hetlioz (tasimelteon) / Vanda - LARVOL DELTA

VP-VEC-162-3502: Evaluating the Effects of Tasimelteon vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD) (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Vanda Pharmaceuticals | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • CNS Disorders • Delayed Sleep Phase Disorder • Sleep Disorder • Sleep Wake Cycle Disorder

The Effects of Tasimelteon in Participants With REM Behavior Disorder (RBD) (clinicaltrials.gov) - P1 | N=20 | Terminated | Sponsor: Brigham and Women's Hospital | Not yet recruiting ➔ Terminated; Study will not longer be done. Terminated due to sponsor noncompliance.

Trial termination • Behavior Disorders • Mental Retardation • Psychiatry

The Efficacy of Melatonergic Receptor Agonists Used in Clinical Practice in Insomnia Treatment: Melatonin, Tasimelteon, Ramelteon, Agomelatine, and Selected Herbs. (PubMed, Molecules) - "It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep-wake disorders."

Journal • Review • CNS Disorders • Insomnia • Sleep Disorder • Sleep Wake Cycle Disorder

Melatonin agonist tasimelteon (HETLIOZ®) improves sleep in patients with primary insomnia: A multicenter, randomized, double-blind, placebo-controlled trial. (PubMed, PLoS One) - "Tasimelteon improved sleep from the first night of treatment, and the effect continued for the duration of the study. Tasimelteon was well-tolerated with no adverse next-day residual effects observed. The results of the study strongly suggest that tasimelteon may be an effective therapeutic tool in the treatment of individuals with chronic sleep onset insomnia."

Clinical • Journal • CNS Disorders • Insomnia • Sleep Disorder

The Cyclical Daytime Sleeper: A Rare Case of a Sighted Teenager with Non-24-Hour Sleep-Wake Disorder (WSS 2025) - "When symptoms did not improve, the patient was started on various hypnotics including clonidine to help with sleep. N24SWD is commonly seen in blind individuals affecting up to 50% of that population. It is very rare in sighted individuals, and may be harder to discern when confounded with conditions like ADHD or poor sleep hygiene. Having patients complete a sleep diary is a cost effective and low investment intervention that may elucidate their condition and ensure timely treatment."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Fatigue • Insomnia • Movement Disorders • Pediatrics • Psychiatry • Restless Legs Syndrome • Sleep Disorder • Sleep Wake Cycle Disorder

Assessment of drug-related migraine in a real-world large-scale database. (PubMed, Front Pharmacol) - "The highest-risk agents included lorcaserin (BCPNN = 3.33), tasimelteon (3.20), and botulinum toxin type A (3.06). Given the public health burden of migraine, pharmacovigilance efforts should incorporate such findings to mitigate iatrogenic risks. Further prospective studies are warranted to establish causal mechanisms and optimize therapeutic decision-making."

Journal • Real-world evidence • CNS Disorders • Migraine • Pain

Neprilysin regulates the progression of glioblastoma: an in-vitro study using siRNA mediated gene silencing and HDAC1 mediated upregulation of neprilysin in U87 MG cells. (PubMed, Mol Cell Biochem) - "Neprilysin (NEP) is a neutral endopeptidase that has gained attention due to its ability to cleave diverse peptides such as fibroblast growth factor-2 (FGF-2), insulin-like growth factors (IGFs), substance P, amyloid-β, thymopentin etc. NEP plays an important role in the functioning of the central nervous system, cardiovascular system, and in pathologies such as Alzheimer's disease, hypertension, and various cancers...Further, in-vitro scratch assays were performed on U87 MG cells to understand the effect of NEP silencing, as well as its upregulation using certain HDAC1 inhibitors identified through in-silico studies (melphalan, tasimelteon and panobinostat), to study the cancer progression...These results suggest an inverse correlation between the NEP levels and GBM proliferation. The tumor suppression exhibited by NEP could be attributed to its degradation of mitogenic proteins such as FGF-2, IGFs etc. In conclusion, NEP can be a promising biomarker and a drug..."

Journal • Preclinical • Alzheimer's Disease • Brain Cancer • Cardiovascular • CNS Disorders • Glioblastoma • Hypertension • Lung Cancer • Oncology • Solid Tumor • FGF2 • HDAC1

Protective effects of tasimelteon on kidney injury in a traumatic brain injury rat model: a histopathological and immunohistochemical study. (PubMed, Eur J Trauma Emerg Surg) - No abstract available

Journal • Preclinical • CNS Disorders • Renal Disease • Vascular Neurology

Genetic Variants Associated With Tst and Lps in Insomnia Patients: Whole Genome Sequencing Study (APA 2025) - "Methods Samples were obtained from adults (ages 18-70) with primary insomnia participating in a randomized, double-blind, placebo-controlled, multi-center study investigated 20 mg or 50 mg tasimelteon vs placebo in 322 patients over 5-weeks of treatment, using polysomnography measures of sleep...Interestingly, DAB1 variants were reported in the largest GWAS of insomnia on UK biobank. Conclusions In this work, we identified potential insomnia loci associated with TST and LPS that further shed light upon understanding of the pathophysiology of insomnia disorder."

Clinical • Whole genome sequencing • CNS Disorders • Developmental Disorders • Fatigue • Infectious Disease • Insomnia • Psychiatry • Schizophrenia • Sleep Disorder • GRIK2

Vanda Pharmaceuticals Reports First Quarter 2025 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $50.0 million in the first quarter of 2025, a 5% increase compared to $47.5 million in the first quarter of 2024. Fanapt net product sales were $23.5 million in the first quarter of 2025, a 14% increase compared to $20.6 million in the first quarter of 2024. HETLIOZ net product sales were $20.9 million in the first quarter of 2025, a 4% increase compared to $20.1 million in the first quarter of 2024. PONVORY net product sales were $5.6 million in the first quarter of 2025, a decrease of 18% compared to $6.8 million in the first quarter of 2024."

Sales • Bipolar Disorder • Multiple Sclerosis • Sleep Disorder • Sleep Wake Cycle Disorder

Evaluating the Effects of Tasimelteon vs. Placebo in Treating Pediatric Insomnia (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Vanda Pharmaceuticals

New P3 trial • CNS Disorders • Insomnia • Pediatrics • Sleep Disorder

Nitrogen Insertion via Asymmetric Condensation and Chirality Transfer: A Stereodivergent Entry to Cyanocyclopropanes. (PubMed, Angew Chem Int Ed Engl) - "This unusual ring contraction is triggered by strong base and permits an axial-to-point chirality transfer with good enantiospecificity (up to 98% es). Fine-tuning the reaction parameters enables stereodivergent access to both diastereomers of the cyanocyclopropanes, and the utility of this method is demonstrated through the formal synthesis of the drug Tasimelteon."

Journal

Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $53.2 million in the fourth quarter of 2024, a 17% increase compared to $45.3 million in the fourth quarter of 2023 and a 12% increase compared to $47.7 million in the third quarter of 2024."

Sales • CNS Disorders

Assessment of adverse events of tasimelteon: a real-world pharmacovigilance study based on FAERS. (PubMed, Expert Opin Drug Saf) - "This study revealed the characteristics of tasimelteon-associated adverse drug reactions, improved understanding of drug safety, and provided valuable signals for optimizing drug use regimens. Additional large-scale prospective studies remain necessary in the future."

Adverse events • Journal • Real-world evidence • CNS Disorders • Insomnia • Mental Retardation • Psychiatry • Sleep Disorder • Sleep Wake Cycle Disorder

Effects of Tasimelteon Treatment on Traumatic Brain Injury Through NRF-2/HO-1 and RIPK1/RIPK3/MLKL Pathways in Rats. (PubMed, Mol Neurobiol) - "However, Tasi treatment reversed all these findings. Tasi protected against brain injury through the NRF-2/HO-1 and RIPK1/RIPK3/MLKL pathways in rats with TBI."

Journal • Preclinical • CNS Disorders • Hematological Disorders • Oncology • Vascular Neurology • CASP3 • HMOX1 • IFNG • MLKL • RIPK1 • RIPK3 • TNFA

Evaluating the Effects of Tasimelteon Vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD) and the CRY1Δ11 Variant (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Vanda Pharmaceuticals

New P3 trial • CNS Disorders • Delayed Sleep Phase Disorder • Sleep Disorder • Sleep Wake Cycle Disorder

VP-VEC-162-3502: Evaluating the Effects of Tasimelteon Vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD) (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Vanda Pharmaceuticals | N=300 ➔ 70 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Enrollment change • Trial primary completion date • CNS Disorders • Delayed Sleep Phase Disorder • Sleep Disorder • Sleep Wake Cycle Disorder

Relationship Between Melatonin Receptor Agonists and Parkinson's Disease. (PubMed, J Pineal Res) - "The target drugs were melatonin receptor agonists including ramelteon, tasimelteon, and agomelatine. In contrast, agomelatine was shown to be positively correlated with Parkinson's disease. These results should be used in research to develop drugs for the treatment of Parkinson's disease, fully considering the limitations of the spontaneous reporting system."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

An in silico drug repurposing approach to identify HDAC1 inhibitors against glioblastoma. (PubMed, J Biomol Struct Dyn) - "The three most active drugs from the MD simulations- ZINC22010649 (Panobinostat), ZINC4392649 (Tasimelteon) and ZINC1673 (Melphalan), were tested on C6 and U87 MG glioblastoma cells for cytotoxicity and HDAC1 protein levels using western blot analysis. Among the three drugs, Panobinostat exhibited potent cytotoxic action and showed a significant reduction in the HDAC1 protein levels.Communicated by Ramaswamy H. Sarma."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Evaluating the Effects of Tasimelteon vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD) (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Vanda Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Delayed Sleep Phase Disorder • Sleep Disorder • Sleep Wake Cycle Disorder

Safety Study of Tasimelteon for Treatment of Non-24-Hour-Sleep-Wake Disorder in Blind Individuals With No Light Perception (clinicaltrials.gov) - P3 | N=140 | Active, not recruiting | Sponsor: Vanda Pharmaceuticals | Unknown status ➔ Active, not recruiting | Trial completion date: Dec 2018 ➔ Dec 2024 | Trial primary completion date: Dec 2018 ➔ Dec 2024

Enrollment closed • Trial completion date • Trial primary completion date • Sleep Disorder • Sleep Wake Cycle Disorder

Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Vanda Pharmaceuticals | Trial completion date: Jul 2023 ➔ Jul 2025 | Trial primary completion date: Jul 2022 ➔ Jul 2025

Trial completion date • Trial primary completion date • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Sleep Disorder

Study of the Pharmacokinetics and Safety of Tasimelteon in Children and Adolescents (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vanda Pharmaceuticals | Unknown status ➔ Completed

Trial completion • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Sleep Disorder • Sleep Wake Cycle Disorder

Bioequivalence Study Between Tasimelteon Capsule Formulation and Liquid Suspension Formulation in Healthy Volunteers (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Vanda Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion

Improvement in non-24-h sleep-wake rhythm disorder in a sighted individual treated with a melatonin receptor agonist. (PubMed, Sleep Med) - "Follow-up actigraphy showed marked resolution of phase delay with an average of five hours of sleep. The case demonstrates that tasimelteon is a possible treatment for N24SWD in sighted individuals."

Journal • CNS Disorders • Insomnia • Sleep Disorder