Hetlioz (tasimelteon) / Vanda - LARVOL DELTA

Circadian rhythm in platelet: an emerging therapeutic target in human diseases. (PubMed, Front Physiol) - "Third, circadian-targeting drugs including tasimelteon, ramelteon, agomelatine, SR9009, VTP-43742, and PF-670462 offer novel therapeutic strategies for rhythm-related disorders. This review highlights the circadian regulation of platelets as an emerging therapeutic target in human diseases."

Journal • Review • Cardiovascular • CNS Disorders • Hematological Disorders • Metabolic Disorders • Thrombosis • NR1D1 • RHOA

VP-VEC-162-3502: Evaluating the Effects of Tasimelteon vs. Placebo in Delayed Sleep-Wake Phase Disorder (DSWPD) (clinicaltrials.gov) - P3 | N=70 | Active, not recruiting | Sponsor: Vanda Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2026 ➔ Sep 2026 | Trial primary completion date: Jun 2026 ➔ Sep 2026

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

Tasimelteon inhibits glioma proliferation by inducing ferroptosis via the SP1/ACSL4 pathway. (PubMed, Cell Oncol (Dordr)) - "Tasimelteon inhibits glioma growth by inducing ferroptosis via the SP1/ACSL4 pathway, offering a novel therapeutic approach."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • ACSL4

VP-VEC-162-3202: Open label safety study of tasimelteon indicated in the treatment of blind individuals with no light perception having problems synchronizing their internal clock with the 24- hour light-dark cycle. (clinicaltrialsregister.eu) - P2/3 | N=140 | Active, not recruiting | Sponsor: Vanda Pharmaceuticals Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Sleep Disorder • Sleep Wake Cycle Disorder

Evaluating Whether Melatonin Impacts Postoperative Sleep Following Total Joint Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, Cureus) - "A search was performed utilizing the Boolean search phrase "(melatonin OR ramelteon OR tasimelteon OR agomelatine) AND (joint OR hip OR knee) AND (replacement OR arthroplasty)." Sleep duration, nightly awakenings, and patient-reported sleep outcomes were recorded when available. Melatonin does not appear to have a significant impact on postoperative sleep following TJA. Further investigation is warranted to address other factors, such as pain and environmental disturbances, to improve sleep quality."

Journal • Retrospective data • Review • CNS Disorders • Orthopedics • Pain • Psychiatry

Design of experiments and bioanalytical LC-MS/MS method for analysis of melatonin and tasimelteon in rat brain homogenate with whiteness assessment. (PubMed, BMC Chem) - "Chromatographic analyses were conducted in isocratic mode, with Citalopram selected as an appropriate internal standard. The total run time was 3 min, with retention time for Melatonin and Tasimelteon at 1.9 and 2.5 min, respectively, achieving effective chromatographic separation under optimum conditions. The Red Green Blue 12 score for whiteness was determined to be 79.2%."

Journal • Preclinical • CNS Disorders • Sleep Disorder

Evaluating the Effects of Tasimelteon vs. Placebo in Treating Pediatric Insomnia (clinicaltrials.gov) - P3 | N=420 | Recruiting | Sponsor: Vanda Pharmaceuticals | N=90 ➔ 420

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

Evaluating the Effects of Tasimelteon vs. Placebo in Treating Pediatric Insomnia (clinicaltrials.gov) - P3 | N=90 | Recruiting | Sponsor: Vanda Pharmaceuticals | Not yet recruiting ➔ Recruiting | N=50 ➔ 90

Enrollment change • Enrollment open • CNS Disorders • Insomnia • Pediatrics • Sleep Disorder

Refusal of a change to the marketing authorisation for Hetlioz (tasimelteon) - Re-examination confirms refusal (European Medicines Agency) - "The change concerned an extension of indication to include the treatment of nighttime sleep disturbance in children aged 3 to 15 years with Smith-Magenis syndrome."

CHMP • Genetic Disorders

Analysis of Tasimelteon in Pharmaceutical Formulations and Bulk Based on Design-Based Quality Approach by HPLC and Greenness Evaluation of the Method. (PubMed, J Chromatogr Sci) - "The internal standard that was deemed most suitable was agomelatine, at a concentration of 33.0 μg/mL. In addition, the environmental sustainability of the method was proved using different analytical greenness metrics as National Environmental Methods Index, analytical eco-scale, Analytical Greenness Metric and Green Analytical Procedure Index for evaluating its greenness. The applicability of the method was demonstrated in the analysis of Hetlioz® pseudo formulation."

Journal

VP-VEC-162-3108: Evaluating the Effects of Tasimelteon vs. Placebo in Treating Pediatric Insomnia (clinicaltrialsregister.eu) - P2/3 | N=50 | Not yet recruiting | Sponsor: Vanda Pharmaceuticals Netherlands B.V., Vanda Pharmaceuticals Inc.

New P2/3 trial • CNS Disorders • Insomnia • Pediatrics • Sleep Disorder

On January 8, 2026, Vanda announced that it had received a decision letter from the FDA Center for Drug Evaluation and Research (CDER) concluding that the supplemental New Drug Application (sNDA) for HETLIOZ (tasimelteon) for the treatment of jet lag disorder cannot be approved in the current form. (PRNewswire) - "This letter followed CDER's re-review of the jet lag sNDA under Vanda's collaborative framework agreement with the FDA. Vanda has requested that the FDA Commissioner resume hearing proceedings."

CRL • Sleep Wake Cycle Disorder

Vanda Pharmaceuticals Reports…Full Year 2025 Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $216.1 million for the full year 2025, a 9% increase compared to $198.8 million for the full year 2024. Fanapt net product sales were $117.3 million for the full year 2025, a 24% increase compared to $94.3 million for the full year 2024. HETLIOZ net product sales were $71.4 million for the full year 2025, a 7% decrease compared to $76.7 million for the full year 2024. PONVORY net product sales were $27.4 million for the full year 2025, a 2% decrease compared to $27.8 million for the full year 2024."

Commercial • Bipolar Disorder • Mood Disorders • Multiple Sclerosis • Psychiatry • Schizophrenia • Sleep Wake Cycle Disorder

Vanda Pharmaceuticals Reports Fourth Quarter…Financial Results (PRNewswire) - "Total net product sales from Fanapt, HETLIOZ and PONVORY were $57.2 million in the fourth quarter of 2025, an 8% increase compared to $53.2 million in the fourth quarter of 2024. Fanapt net product sales were $33.2 million in the fourth quarter of 2025, a 25% increase compared to $26.6 million in the fourth quarter of 2024. HETLIOZ net product sales were $16.4 million in the fourth quarter of 2025, an 18% decrease compared to $20.0 million in the fourth quarter of 2024. PONVORY net product sales were $7.6 million in the fourth quarter of 2025, a 17% increase compared to $6.5 million in the fourth quarter of 2024."

Commercial • Sales • Bipolar Disorder • Mood Disorders • Multiple Sclerosis • Psychiatry • Schizophrenia • Sleep Wake Cycle Disorder

Vanda Pharmaceuticals Announces Receipt of FDA Decision Letter on HETLIOZ Supplemental New Drug Application for Jet Lag Disorder (Yahoo Finance) - "This letter stems from CDER's agreed re-review of the jet lag application under the October 1 collaborative framework agreement...As previously announced, in August 2025 the D.C. Circuit set aside a prior FDA refusal to approve HETLIOZ for jet lag disorder, describing Vanda's evidence as 'specific, reasoned, and rooted in evidence' and the FDA's prior review as "cursory," while noting statistically significant improvements on primary endpoints across trials."

FDA event • CNS Disorders

Serial patent litigation: an emerging strategy to delay entry of generic competition. (PubMed, Health Aff Sch) - "In the case of Astellas's overactive bladder drug mirabegron (Myrbetriq), after an initial Hatch-Waxman case settled in 2020 with generic entry expected in 2024, Astellas pursued 4 additional lawsuits, each built on new but substantively indistinguishable patents. These tactics have delayed broad competition, leaving only 2 firms to launch in 2024 under the threat of massive damages. Similar patterns are observed with other drugs, including bimatoprost (Latisse), aflibercept (Eylea), and tasimelteon (Hetlioz)."

Journal • Overactive Bladder

Can We Develop Glioma Subtype-Specific Precision Medicines? An Integrative Machine Learning Pipeline for Biomarker Discovery and Drug Repurposing for Glioblastoma and Low-Grade Glioma. (PubMed, OMICS) - "Repurposed drug candidates were then predicted via signature-based prioritization and evaluated using molecular docking simulations, revealing six promising compounds for GBM (vandetanib, capecitabine, melatonin, agomelatine, ramelteon, and tasimelteon) and one for LGG (ambroxol). This study demonstrates the utility of combining class-balancing, feature selection, and drug repurposing pipelines to uncover clinically relevant glioma biomarkers and therapeutic candidates, thus providing a computational foundation for future experimental and translational validation in these brain cancers and neuro-oncology."

Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ANK3

Exploring Sleep Challenges and Interventions in Children with a Vision Impairment: A Scoping Review. (PubMed, Children (Basel)) - "Other pharmacological options, such as tasimelteon and vitamin B12, were rarely reported... Overall, the evidence base is small, heterogeneous, and methodologically limited. Further research is needed to develop and carefully test non-pharmacological approaches, and to compare them directly with pharmacological treatments, to provide families and clinicians with effective and sustainable options."

Journal • Review • Novel Coronavirus Disease • 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 | 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