Lemborexant
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Lemborexant: From Insomnia to Sleep Disorder (Initiating and Maintaining Sleep)
One-Sentence Summary
Lemborexant is a dual orexin receptor antagonist originally used to treat insomnia. The TxGNN model predicts it may be effective for sleep disorder, initiating and maintaining sleep, which is closely related to its existing indication. This direction is supported by 19 publications (including several network meta-analyses and a Phase 3 randomised trial), but no registered clinical trials were found in the data compiled for this report.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Insomnia (the Singapore licence records contain no indication text; the original indication comes from the knowledge graph) |
| Predicted New Indication | Sleep disorder, initiating and maintaining sleep |
| TxGNN Prediction Score | 99.75% |
| Evidence Level | L1 (as assigned in the compiled data; see the note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Note: This is not a true repurposing case. "Sleep disorder, initiating and maintaining sleep" is essentially another name for insomnia, the drug's existing indication. The L1 grade rests on the strength of the published literature (network meta-analyses and Phase 3 trials). No completed Phase 3 trials were registered in the data compiled here, so the level should be read with that caveat.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. The literature, however, consistently describes lemborexant as an orally administered dual orexin receptor antagonist. It competitively and reversibly blocks OX1R and OX2R, with higher affinity for OX2R.
Orexin is a key neuropeptide that promotes wakefulness and arousal. Insomnia is associated with a state of hyperarousal. Blocking orexin signalling reduces this wake drive, which helps patients fall asleep and stay asleep. This matches the predicted indication of difficulty initiating and maintaining sleep.
The predicted disease is a description of the same clinical problem as the original indication. The prediction is therefore highly plausible, but it adds little new information. Lemborexant was first approved in the USA in December 2019 for adults with difficulty with sleep onset and/or sleep maintenance.
Clinical Trial Evidence
Currently no related clinical trials are registered in the data compiled for this report.
The publications below report completed or ongoing trials:
- SUNRISE 2 (PMID 32585700): Phase 3 randomised trial of long-term efficacy and tolerability versus placebo.
- Older adults study (PMID 31880796): Phase 3 randomised trial versus placebo and zolpidem extended release.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32585700 | 2020 | Phase 3 RCT (SUNRISE 2) | Sleep | Long-term efficacy and tolerability of lemborexant versus placebo in adults with insomnia disorder |
| 31880796 | 2019 | Phase 3 RCT | JAMA Netw Open | Lemborexant compared with placebo and zolpidem extended release in older adults with insomnia |
| 40555730 | 2025 | Network meta-analysis | Transl Psychiatry | Efficacy and safety of daridorexant, lemborexant and suvorexant compared |
| 35843245 | 2022 | Network meta-analysis | Lancet | Comparative effects of drugs for acute and long-term insomnia management in adults |
| 36701954 | 2023 | Network meta-analysis | Sleep Med Rev | Efficacy and tolerability ranking of 20 insomnia drugs in adults |
| 36947394 | 2023 | Network meta-analysis | Drugs | Comparative effectiveness and safety of insomnia drugs across 153 randomised trials |
| 34121443 | 2021 | Network meta-analysis | J Manag Care Spec Pharm | Efficacy and safety of lemborexant compared with other insomnia treatments |
| 37950346 | 2024 | Meta-analysis | Sleep | Clinical safety of DORAs, with a focus on narcolepsy-like symptoms |
| 41071053 | 2025 | Review | Expert Rev Clin Pharmacol | Comprehensive overview of lemborexant in insomnia treatment |
| 32096020 | 2020 | Drug profile | Drugs | Lemborexant (Dayvigo) first approval summary and pharmacology |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16320P | DAYVIGO Film-Coated Tablet 5 mg | Film-coated tablet | Not listed in the licence record |
| SIN16321P | DAYVIGO Film-Coated Tablet 10 mg | Film-coated tablet | Not listed in the licence record |
Both licences are valid single-ingredient products from Eisai Manufacturing Limited, for oral use.
Safety Considerations
- Knowledge-graph contraindication signals (from the knowledge graph, not from label text): narcolepsy, narcolepsy-cataplexy syndrome, central nervous system disease, Balo concentric sclerosis, and X-linked adrenoleukodystrophy. The narcolepsy signal fits the drug's mechanism, and a meta-analysis (PMID 37950346) specifically examined narcolepsy-like symptoms with DORAs.
- Drug Interactions: The interaction screen returned 100 interactions in total. Major-level examples include:
- Clarithromycin, clotrimazole and aprepitant
- Cimetidine and ranitidine
- Morphine, including the liposomal form
Moderate-level examples include bupropion, dexamethasone, pioglitazone, metoclopramide, dronabinol and nabilone. Combining this drug with other CNS depressants, such as opioids and cannabinoids, deserves particular attention. Several of the Major interactors are also enzyme-pathway inhibitors, so exposure may rise when they are co-administered.
For warnings and contraindications from the label, please refer to the package insert.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The predicted indication is effectively the drug's existing indication, and it is supported by Phase 3 randomised trials and multiple network meta-analyses. Lemborexant is already marketed in Singapore with two valid licences. Because the Singapore licence records do not show an indication, and the label safety information is missing, the decision carries guardrails.
To proceed, the following is needed:
- Obtain the HSA package insert to confirm the approved indication, warnings and contraindications (this is a blocking gap for safety screening)
- Obtain detailed mechanism of action data from DrugBank
- Confirm that the Singapore approved indication matches the predicted indication
- Establish a monitoring plan for patients on CYP-inhibiting drugs or other CNS depressants, and for patients with narcolepsy-related conditions
Other Predictions Reviewed (Not Recommended for Advancement)
| Predicted Indication | TxGNN Score | Evidence Level | Decision | Comment | |------|------|------|------|------| | Anxiety disorder | 79.34% | L4 | Research Question | Only preclinical work (PMID 42532180) and insomnia-population studies with comorbid anxiety or depression. No proven anxiety indication. | | Acute encephalopathy with biphasic seizures and late reduced diffusion | 97.38% | L5 | Hold | Model prediction only; no mechanistic link | | Agoraphobia | 88.27% | L5 | Hold | Prediction only; no studies | | Childhood absence epilepsy | 86.66% | L5 | Hold | No supporting evidence; seizure safety would need assessment | | Faciodigitogenital syndrome | 86.19% | L5 | Hold | Likely a knowledge-graph artefact | | Wernicke-Korsakoff syndrome | 86.16% | L5 | Hold | No evidence; sedative safety concerns | | Benign paroxysmal torticollis of infancy | 85.98% | L5 | Hold | No evidence; no paediatric use established | | Inherited prion disease | 85.71% | L5 | Hold | No evidence of any benefit | | Attention deficit-hyperactivity disorder | 83.04% | L5 | Hold | No evidence; mechanism not expected to treat core symptoms |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.