Tasimelteon

證據等級: L5

預測適應症: 10 個

Tasimelteon: From Non-24-Hour Sleep-Wake Disorder to Insomnia

One-Sentence Summary

Tasimelteon is a selective MT1/MT2 melatonin receptor agonist, originally approved by the FDA for Non-24-Hour Sleep-Wake Disorder (Non-24) in totally blind individuals. The TxGNN model predicts it may be effective for Insomnia, with 4 clinical trials (including 2 completed Phase 3 studies) and 6 publications currently supporting this direction.

Note on candidate selection: TxGNN rank 1 (bilateral parasagittal parieto-occipital polymicrogyria, score 99.48%) is classified as L5/Hold due to absent mechanistic linkage and zero supporting evidence. This report focuses on rank 2 (insomnia, score 99.47%), which carries L1 evidence and the highest decision stage (S3), representing the most actionable repurposing candidate.

Quick Overview

Item	Content
Original Indication	Non-24-Hour Sleep-Wake Disorder
Predicted New Indication	Insomnia
TxGNN Prediction Score	99.47%
Evidence Level	L1
US Market Status	No records found in regulatory database
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in this Evidence Pack (Data Gap DG002). Based on known information, Tasimelteon is a selective melatonin receptor agonist (MT1/MT2) that acts on the suprachiasmatic nucleus (SCN) — the brain’s master circadian pacemaker. By binding MT1 and MT2 receptors in the SCN, it phase-shifts the circadian clock, reduces sleep onset latency, and re-entrains the biological sleep-wake cycle to the 24-hour day.

Non-24-Hour Sleep-Wake Disorder and insomnia share a common mechanistic root: dysregulation of circadian timing. Non-24 represents an extreme failure to entrain to the light-dark cycle, while general insomnia frequently involves circadian phase misalignment and blunted melatonin rhythm. Because Tasimelteon acts upstream at the circadian pacemaker rather than as a sedative-hypnotic, it is mechanistically plausible that the same receptor-level action would improve sleep onset and maintenance in primary insomnia patients.

This prediction is strongly reinforced by two lines of evidence. First, a completed Phase 3 RCT (NCT00548340, n=322) directly compared Tasimelteon versus placebo in patients with primary insomnia — the highest grade of human clinical evidence. Second, the FDA-approved comparator ramelteon (also an MT1/MT2 agonist, approved 2005) is already indicated for insomnia, providing same-class proof-of-concept. A large ongoing Phase 3 pediatric trial (NCT06953869, n=420) further signals continued investment in this indication.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00548340	Phase 3	Completed	322	Multicenter double-blind RCT comparing Tasimelteon 20 mg and 50 mg vs. placebo over 5 weeks in primary insomnia — the highest-grade direct evidence for this indication
NCT06953869	Phase 3	Recruiting	420	Multicenter double-blind RCT of Tasimelteon vs. placebo in pediatric insomnia; large-scale ongoing trial, expected completion January 2028
NCT03291041	Phase 2	Completed	25	Double-blind proof-of-concept study in jet lag disorder (proxy circadian misalignment model); indirectly supports sleep-onset efficacy via circadian resetting mechanism
NCT05922995	Early Phase 1	Terminated	20	Open-label pilot in REM Behavior Disorder assessing insomnia symptom scores (ISI, PSQI); terminated early with limited enrollment — safety reference only, low methodological weight

Literature Evidence

PMID	Year	Type	Journal	Key Findings
25207602	2014	Narrative Review	Int J Mol Sci	Reviewed efficacy and safety of four melatonin receptor agonists (including Tasimelteon) for insomnia and circadian disorders; highlighted complementary mechanisms across the drug class
24228714	2014	Review	J Med Chem	Comprehensive MT1/MT2 receptor pharmacology review; positioned Tasimelteon as a high-affinity non-selective agonist, distinguishing it from sedative-hypnotics for sleep-wake disorder applications
19557144	2009	Review	Neuropsychiatr Dis Treat	Compared melatoninergic agonists vs. classical hypnotics for insomnia; reported Tasimelteon reduced sleep onset latency in Phase 2/3 trials with a favorable adverse-effect profile
35585820	2023	Review	Curr Drug Saf	Discussed Tasimelteon’s role in Alzheimer’s-associated insomnia and neurodegenerative sleep disruption; contextualizes potential beyond Non-24
22010042	2011	Review	Ther Adv Neurol Disord	Examined melatonin agonists in Parkinson’s disease sleep disorders; Tasimelteon discussed as mechanistically relevant to REM-related insomnia components
22167135	2011	Review	Neuro Endocrinol Lett	Linked circadian rhythm disruption in obesity with insomnia pathophysiology; proposed melatonin receptor agonists as resynchronizing agents for metabolic-comorbid insomnia

US Market Information

No FDA authorization records for Tasimelteon were retrieved in the regulatory database query (2026-03-25, result count: 0). The regulatory data gap (DG001) — covering package insert warnings and contraindications — is classified as Blocking severity.

For reference: Tasimelteon is commercially available in the United States under the brand name Hetlioz (Vanda Pharmaceuticals), FDA-approved for Non-24-Hour Sleep-Wake Disorder. Verification against the official FDA database is recommended before proceeding.

Safety Considerations

Please refer to the package insert for safety information.

All safety fields (key warnings, contraindications, drug-drug interactions) were returned as data gaps or not found in the 2026-03-25 query. Obtaining the full TFDA/FDA package insert is a Blocking prerequisite (DG001) before safety evaluation can proceed.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A completed Phase 3 double-blind RCT (NCT00548340, n=322) directly supports Tasimelteon for primary insomnia at L1 evidence level, and the FDA-approved class comparator ramelteon demonstrates that MT1/MT2 agonism is a validated mechanism for this indication. The ongoing pediatric Phase 3 trial (NCT06953869, n=420) further confirms industry confidence in this repurposing direction.

To proceed, the following is needed:

[Blocking] Obtain full FDA/TFDA package insert to complete safety evaluation (warnings, contraindications, special population precautions) — Data Gap DG001
[High] Retrieve DrugBank MOA documentation for mechanistic linkage analysis — Data Gap DG002
[Required] Drug-drug interaction profile — current DDI query returned no records; manual lookup or clinical pharmacology review required
[Monitoring] Await results from NCT06953869 (pediatric Phase 3, expected completion January 2028) to support pediatric indication extension
[Strategic] Confirm US FDA regulatory pathway: if targeting insomnia as a new indication, assess whether a supplemental NDA or 505(b)(2) pathway is appropriate given the existing Non-24 approval
[Regulatory] Evaluate Taiwan market entry feasibility given current zero-license status in TFDA database
Disclaimer

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