Perampanel
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Perampanel: From Epilepsy (Partial-Onset Seizures) to Visual Epilepsy
One-Sentence Summary
Perampanel is a selective, non-competitive AMPA receptor antagonist used for partial-onset and generalized tonic-clonic seizures in epilepsy (per literature evidence; official indication text is not available in this data pack). The TxGNN model predicts it may also be effective for Visual Epilepsy, a photosensitive/visually-triggered reflex seizure subtype, with 3 clinical trials and 20 publications currently available as supporting context — though none directly study visual epilepsy as a distinct entity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available from regulatory license data (0 licenses on file); per literature, perampanel is indicated for partial-onset seizures (adjunctive/monotherapy) and primary generalized tonic-clonic seizures |
| Predicted New Indication | Visual Epilepsy |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| US Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in this evidence pack (flagged as a data gap). Based on the supporting literature retrieved, perampanel is a selective, non-competitive AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist — the first drug in its class approved as an anti-epileptic agent. It works by inhibiting glutamate-mediated postsynaptic excitation, which underlies its broad-spectrum anticonvulsant activity across multiple seizure types (PMID 24559052, PMID 21635236).
Visual epilepsy is a reflex epilepsy subtype in which seizures are triggered by visual stimuli (e.g., flashing lights, patterns), involving cortical hyperexcitability in occipital/visual pathways. Since AMPA receptors mediate excitatory transmission broadly across the cortex — including visual cortex circuits — there is a plausible mechanistic rationale for perampanel’s efficacy in this reflex seizure subtype, consistent with its demonstrated “broad-spectrum” anticonvulsant profile (PMID 29953584).
However, the clinical trial and literature evidence currently available addresses general epilepsy populations rather than visual/photosensitive epilepsy specifically. One retrieved trial (NCT03653741) did examine visual evoked potentials (VEP) as a neurophysiology endpoint, which is tangentially relevant but not a treatment-efficacy study for visual epilepsy. The prediction should therefore be regarded as mechanistically plausible but not yet clinically validated for this specific indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03780907 | Phase 2 | Completed | 18 | Randomised, double-blind, placebo-controlled tolerability/safety/PK study of E2007 (perampanel) in patients with partial and generalized seizures; not specific to visual epilepsy |
| NCT02900755 | Phase 4 | Completed | 30 | Evaluated perampanel’s effects on cognition and EEG in epilepsy patients; general refractory partial-onset seizure population |
| NCT03653741 | Phase 4 | Completed | 12 | Assessed perampanel’s effect on neurophysiology tests (EEG, SEP, BAEP, and visual evoked potential/VEP) in healthy volunteers; relevant to visual pathway function but not a treatment trial for visual epilepsy |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37684052 | 2023 | Review | BMJ | Overview of anti-seizure medication management (incl. perampanel) during pregnancy/lactation; general safety context |
| 36218253 | 2022 | Review | Revista de Neurología | Pediatric status epilepticus management overview |
| 29898971 | 2018 | Practice Guideline | Neurology | AAN/AES guideline update on efficacy/tolerability of new AEDs for new-onset epilepsy |
| 36034267 | 2022 | Real-world study | Frontiers in Neurology | Real-life effectiveness/tolerability of perampanel as add-on/monotherapy in childhood absence epilepsy |
| 36150304 | 2022 | Review | Epilepsy & Behavior | Review of perampanel monotherapy clinical trial and real-world evidence for focal-onset and generalized tonic-clonic seizures |
| 24559052 | 2014 | Review | Expert Opin Drug Discov | Discovery/development history; approved in 35+ countries as adjunctive therapy for partial-onset seizures |
| 37775491 | 2023 | Observational | Med J Malaysia | Efficacy/safety of adjunctive perampanel in epilepsy patients |
| 37329172 | 2023 | Retrospective cohort | Ann Clin Transl Neurol | Efficacy of perampanel in pediatric epilepsy with known/presumed genetic etiology |
| 37378757 | 2023 | Systematic Review / Network Meta-analysis | J Neurology | ASM comparison (incl. perampanel) for idiopathic generalized epilepsies |
| 37292124 | 2023 | Retrospective cohort | Frontiers in Neurology | Effectiveness/tolerability of perampanel monotherapy in newly diagnosed pediatric focal epilepsy |
US Market Information
Perampanel is currently recorded as Not Marketed in this regulatory dataset, with 0 licenses on file. No NDA, product name, or approved indication text is available for this evidence pack.
Safety Considerations
Please refer to the package insert for safety information. (No key warnings, contraindications, or drug interaction data were available in this evidence pack — all fields returned as data gaps.)
Conclusion and Next Steps
Decision: Hold
Rationale: A blocking data gap exists for TFDA/label warnings and contraindications, which prevents even an initial (S1) safety evaluation. In addition, while perampanel’s AMPA-antagonist mechanism offers a plausible rationale for visual epilepsy, all available clinical trial and literature evidence addresses general epilepsy populations rather than the visual/photosensitive subtype specifically — evidence level is best characterized as L4 (mechanistic/indirect), not yet clinical proof-of-concept for this indication.
To proceed, the following is needed:
- TFDA/FDA label data — warnings, contraindications, and drug interactions (DG001, Blocking)
- Confirmed mechanism of action documentation from DrugBank (DG002)
- Disease-specific clinical evidence (case series, observational studies, or trials) evaluating perampanel in visual/photosensitive epilepsy specifically
- Confirmation of original indication and regulatory license status, since no licenses are currently on file
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.