Tasimelteon

證據等級: L5

預測適應症: 10 個

Tasimelteon: From No Danish Registration to Insomnia (Circadian Rhythm Sleep Disorder)

One-Sentence Summary

Tasimelteon is a melatonin MT1/MT2 receptor agonist with no current marketing authorisation in Denmark and no local approved-indication data on file. The TxGNN model’s most clinically credible signal points to Insomnia (disease), a mechanistically on-target use supported by 4 clinical trials (including a completed pivotal Phase 3 RCT) and 6 publications. Several other TxGNN-ranked candidates (e.g. polymicrogyria, ALS, axial spondylometaphyseal dysplasia) carry similarly high raw scores but have zero supporting trials or literature and are explicitly flagged in the source data as likely graph noise — they are not covered further in this report.

Quick Overview

Item	Content
Original Indication	Not on file — Tasimelteon has no marketing authorisation in Denmark, so no approved-indication text exists in the regulatory data
Predicted New Indication	Insomnia (disease)
TxGNN Prediction Score	99.47%
Evidence Level	L1
Denmark Market Status	Not Marketed
Number of Marketing Authorisations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Tasimelteon is a melatonin MT1/MT2 receptor agonist that acts directly on the suprachiasmatic nucleus (the body’s central circadian pacemaker) to shift circadian phase and promote sleep onset. This is described consistently across the supporting literature and in the model’s own rationale text.

Because this mechanism directly governs the sleep-wake cycle, the “predicted” indication of insomnia is not a distant cross-mechanism hypothesis — it is the drug’s core, on-target pharmacology. The evidence pack itself notes this is “屬藥理機轉核心適應症範疇，非跨機轉推論” (a core mechanism-consistent indication, not a repurposing inference), which is consistent with the drug class already being used clinically for insomnia and other circadian rhythm sleep-wake disorders.

This is reinforced by a completed Phase 3, double-blind, placebo-controlled trial (n=322) and an actively recruiting Phase 3 pediatric trial (n=420), showing sustained clinical development interest in this indication area — evidence considerably stronger than the model score alone would suggest.

Note on other TxGNN candidates: Bilateral parasagittal parieto-occipital polymicrogyria, amyotrophic lateral sclerosis, and axial spondylometaphyseal dysplasia scored similarly high but returned zero clinical trials and zero literature hits. The evidence pack explicitly characterises these as having no known pathophysiological link to melatonin receptor agonism and recommends “Hold” for all of them — they are not analysed further here.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00548340	Phase 3	Completed	322	Multicenter, randomized, double-blind, placebo-controlled trial of VEC-162 (tasimelteon) 20mg/50mg daily vs. placebo over 5 weeks in primary insomnia — pivotal-grade efficacy/safety evidence
NCT06953869	Phase 3	Recruiting	420	Ongoing multicenter, double-blind, randomized study of tasimelteon vs. placebo for pediatric insomnia disorder
NCT03291041	Phase 2	Completed	25	Proof-of-concept study of tasimelteon vs. placebo in travelers with jet lag disorder (adjacent circadian indication)
NCT05922995	Early Phase 1	Terminated	20	Single-center, open-label pilot study of tasimelteon 20mg for REM Behavior Disorder; trial terminated early, low evidentiary weight

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35585820	2023	Review	Current Drug Safety	Discusses melatonin/tasimelteon relevance to Alzheimer’s-related sleep and behavioral disturbance
25207602	2014	Review	International Journal of Molecular Sciences	Reviews efficacy/safety of melatonin receptor agonists (incl. tasimelteon) across insomnia, depression, and circadian rhythm disorders
24228714	2014	Review	Journal of Medicinal Chemistry	Reviews MT1/MT2 receptor pharmacology; identifies tasimelteon as a high-affinity nonselective MT1/MT2 agonist
22010042	2011	Review	Therapeutic Advances in Neurological Disorders	Reviews melatonin/analogs for sleep disturbance and neuroprotection in Parkinson’s disease
22167135	2011	Review	Neuro Endocrinology Letters	Reviews circadian sleep disruption and potential therapeutic value of melatonin in obesity
19557144	2009	Review	Neuropsychiatric Disease and Treatment	Reviews prolonged-release melatonin and synthetic melatoninergic agonists for insomnia management

Denmark Market Information

Tasimelteon is not currently marketed in Denmark — no marketing authorisation (national or centralised/EMA) is on file, and no approved indication text is available.

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A completed Phase 3 RCT (n=322) plus an actively recruiting Phase 3 trial (n=420) provide mechanism-consistent, L1-grade evidence for tasimelteon in insomnia/circadian rhythm sleep disorders. However, the drug has no Danish marketing authorisation and no local safety/label data, so a full risk-benefit assessment cannot yet be completed.

To proceed, the following is needed:

Local safety/label data (key warnings, contraindications) — currently a Blocking data gap preventing safety pre-assessment (S1)
Formal mechanism-of-action documentation (structured MOA field is currently unpopulated, though rationale text confirms MT1/MT2 agonism)
Drug-drug interaction (DDI) data — current query returned no results
A regulatory pathway assessment for Denmark, given zero existing marketing authorisations
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.