Tasimelteon

證據等級: L5

預測適應症: 10 個

Tasimelteon: From Circadian Rhythm Sleep-Wake Regulation to Insomnia

One-Sentence Summary

Tasimelteon (DB09071) is a melatonin MT1/MT2 receptor agonist; this evidence pack scored it against 10 TxGNN-predicted indications, and Insomnia is the only one that reached actionable evidence (evidence level L1, decision stage S3), while the other 9 — including the highest raw TxGNN score (bilateral parasagittal parieto-occipital polymicrogyria) — remain at Hold with no clinical trials or literature support. For insomnia specifically, 4 clinical trials (including one completed Phase 3 RCT, n=322) and 6 publications currently support this direction.

Quick Overview

Item	Content
Original Indication	Not recorded in this data pack (drug not currently marketed in Finland; no license record to source an approved indication text)
Predicted New Indication	Insomnia
TxGNN Prediction Score	99.47%
Evidence Level	L1
Finland Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

DrugBank's mechanism-of-action field is empty in this data pack, but the literature evidence collected alongside it is consistent: tasimelteon is a non-selective MT1/MT2 melatonin receptor agonist that acts on the suprachiasmatic nucleus (SCN), the brain's circadian pacemaker, to phase-shift circadian rhythms and promote sleep onset (PMID 19579175, 24228714, 25207602).

No formal "original indication" is captured in this pack's regulatory data — the drug has no marketing authorization on file in Finland. However, the trial evidence itself points to insomnia as part of tasimelteon's original clinical development scope: the drug's development code, VEC-162, was studied in a completed Phase 3, double-blind, placebo-controlled trial specifically for primary insomnia (NCT00548340, 2007–2008). This suggests the TxGNN prediction is not identifying a novel repurposing signal so much as recovering a well-established, mechanistically direct use of the compound.

Because MT1/MT2 agonism directly targets sleep-onset physiology, the mechanistic rationale for insomnia is strong and requires no cross-indication extrapolation — unlike most of the other 9 candidates in this pack (e.g., ALS, polymicrogyria, skeletal dysplasia), which have no identifiable pathophysiological link to melatonergic signaling and no supporting evidence.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00548340	Phase 3	Completed	322	Randomized, double-blind, placebo-controlled 5-week trial of VEC-162 (tasimelteon) 20 mg/day and 50 mg/day for primary insomnia efficacy and safety
NCT06953869	Phase 3	Recruiting	420	Multicenter, double-blind, randomized trial of tasimelteon vs. placebo in pediatric insomnia disorder; ongoing, completion expected 2028-01
NCT03291041	Phase 2	Completed	25	Proof-of-concept study of tasimelteon vs. placebo in travelers with jet lag disorder (circadian-related sleep disturbance, not classic insomnia)
NCT05922995	Early Phase 1	Terminated	20	Open-label pilot assessing 20 mg tasimelteon on dream enactment and insomnia symptoms (ISI, PSQI, ESS) in REM Behavior Disorder patients

Literature Evidence

PMID	Year	Type	Journal	Key Findings
25207602	2014	Review	International Journal of Molecular Sciences	Reviews therapeutic effects of melatonin receptor agonists (including tasimelteon) on insomnia and comorbid disorders
24228714	2014	Review	Journal of Medicinal Chemistry	Characterizes tasimelteon as a high-affinity non-selective MT1/MT2 agonist; reviews ligands and therapeutic potential
19557144	2009	Review	Neuropsychiatric Disease and Treatment	Discusses synthetic melatoninergic agonists as an approach to insomnia management
35585820	2023	Review	Current Drug Safety	Discusses melatonin and tasimelteon in the context of Alzheimer's disease-associated insomnia
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 melatonin's role in chronobiology of sleep and cytoprotection in obesity

Finland Market Information

Tasimelteon is not currently marketed in Finland — no marketing authorizations are on file (0 licenses).

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A completed Phase 3, placebo-controlled RCT (n=322) directly supports efficacy for primary insomnia, reinforced by a consistent literature base on the MT1/MT2 mechanism and an actively recruiting pediatric Phase 3 trial. However, no Finnish/EU safety labeling (warnings, contraindications, DDI) or confirmed original indication is available in this data pack, so full risk assessment cannot yet proceed to S1 safety clearance.

To proceed, the following is needed:

Package insert / label data (warnings, contraindications, DDI) — currently marked as a Blocking data gap (DG001)
Confirmed original approved indication and regulatory history for tasimelteon
Formal DrugBank mechanism-of-action record to replace the literature-derived MOA used here
Results of the ongoing pediatric Phase 3 trial (NCT06953869, expected completion 2028-01)
Note: the other 9 TxGNN-predicted indications in this pack (including the top-scored polymicrogyria prediction) have no clinical trial or literature support and remain at Hold — no further action recommended on those without new evidence.
Disclaimer

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