Hetlioz (tasimelteon) / Vanda - LARVOL DELTA

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

Vanda Pharmaceuticals Announces FDA Update for supplemental NDA for HETLIOZ in the Treatment of Insomnia (PRNewswire) - "Vanda Pharmaceuticals Inc...announced that on February 4, 2024, it received a notification from the U.S. Food and Drug Administration (FDA) stating that as part of its ongoing review of Vanda's supplemental New Drug Application (sNDA) for HETLIOZ (tasimelteon) in the treatment of insomnia characterized by difficulties with sleep initiation, the FDA has identified deficiencies that preclude discussion of labeling and postmarketing requirements/commitments at this time. No deficiencies were disclosed by the FDA in the notification, and the FDA stated that the notification does not reflect a final decision on the information under review. In a letter to Vanda dated July 17, 2023, the FDA had assigned a Prescription Drug User Fee Act target date of March 4, 2024 for the completion of its review of the sNDA."

PDUFA date • sNDA • CNS Disorders • Insomnia • Sleep Disorder

The Effects of Tasimelteon in Participants With REM Behavior Disorder (RBD) (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Brigham and Women's Hospital

New P1 trial • Behavior Disorders • Mental Retardation • Psychiatry

A Rare Case of Non-24-hour Sleep-Wake Rhythm Disorder in A Sighted Patient (SLEEP 2023) - "She tried melatonin and light therapy for a short time without much of success, she was subsequently started on tasimelteon and the clinical response is to be followed...Some antidepressant are also found to cause potential iatrogenic circadian rhythm sleep disorders. Psychosocial interventions that target stabilizing daily rhythms in patients with concurrent psychiatric illness can be helpful."

Clinical • Bipolar Disorder • Cataplexy • CNS Disorders • Excessive Daytime Sleepiness • Mental Retardation • Mood Disorders • Psychiatry • Restless Legs Syndrome • Sleep Disorder • Sleep Wake Cycle Disorder

Dual Therapy to Treat Circadian Rhythm Disturbance in Unique Genetic Mutation of Smith-Magenis Syndrome (SLEEP 2023) - "Our patient switched to therapy with beta-1 adrenergic antagonist in the mornings and melatonin receptor agonist, tasimelteon, at night with significant improvement...ZBTB18 mutation is a novel mutation in the setting of clinical features of SMS. Conclusion To the authors’ knowledge, this is the first case report of successful combination therapy to optimize treatment of sleep-wake disturbances in patients with SMS."

CNS Disorders • Sleep Disorder • Sleep Wake Cycle Disorder

Non-24-hour Sleep-wake Rhythm Disorder in Sighted Individual Treated With Tasimelteon (ATS 2023) - "Previous interventions included prescription of insomnia medications (melatonin, zolpidem, trazadone) and stimulants (armodafinil, modafinil, methylphenidate, mixed amphetamine salts)...Medications included vortioxetine and quetiapine for his mood disorder...Previous interventions included prescription of insomnia medications (melatonin, zolpidem, trazadone) and stimulants (armodafinil, modafinil, methylphenidate, mixed amphetamine salts)...Medications included vortioxetine and quetiapine for his mood disorder...Blue highlighted areas indicate periods of relatively low actigraphy activity which correspond to sleeping period. Note the dominant sleeping period advances each day of data collection."

Clinical • CNS Disorders • Depression • Insomnia • Mood Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

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ANDA

The Effect of Blindness on Biological Rhythms and the Consequences of Circadian Rhythm Disorder. (PubMed, Turk J Ophthalmol) - "Drug therapy includes melatonin and the melatonin agonist tasimelteon. Diagnosing blind individuals' sleep disorders is also relevant to treatment because they can be improved with the use of melatonin and its analogues or by phototherapy if they have residual vision. Therefore, assessing sleep problems and planning treatment accordingly for individuals presenting with blindness is an important issue for ophthalmologists to keep in mind."

Journal • Anorexia • CNS Disorders • Gastrointestinal Disorder • Mood Disorders • Ophthalmology • Psychiatry • Sleep Disorder • Sleep Wake Cycle Disorder

Sandman Send Me a Dream: Case of Non-24-Hour Sleep-Wake Disorder in a Sighted Pediatric Patient (AAN 2023) - "The patient was initiated on tasimelteon which led to significant improvements in his ability to maintain a consistent bedtime...If not identified, it can lead to long term effects on a child’s life, affecting their development and education. This case also demonstrated the benefits of selective melatonin agonists in the treatment of this condition."

Clinical • Excessive Daytime Sleepiness • Pediatrics • Sleep Disorder • Sleep Wake Cycle Disorder

A Self-Immolative Linker for the pH-Responsive Release of Amides. (PubMed, Molecules) - "Here, we report a general procedure for the preparation of benzylic N-acyl carbamates suitable for masking the amide group in important drugs such as Linezolid, Enzalutamide, or Tasimelteon in good to acceptable yields. These N-acyl carbamates appear to be stable in plasma, while a qualitative analysis of further drug uncage demonstrates that, at pH values of 5.5, a classical 1,6-benzyl elimination mechanism takes place, releasing more than 80% of the drug in 24 h."

Journal

"Absence Of Braille In Generic Hetlioz Label Merits Its Withdrawal, Vanda Lawsuit Argues https://t.co/2o2fd5s03L #PinkSheet" (@PharmaPinkSheet)

Corporate lawsuit

INTENSIVE CARE UNIT USE OF MELATONIN RECEPTOR AGONISTS IMPROVES OUTCOMES IN SEPSIS PATIENTS (SCCM 2023) - "Of note, the effects of melatonin can be activated by melatonin receptor agonists (such as tasimelteon and ramelteon). ICU use of melatonin receptor agonist ramelteon associated with outcome improvements in sepsis patients."

Clinical • CNS Disorders • Critical care • Immunology • Infectious Disease • Inflammation • Septic Shock