Perampanel
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Perampanel: From Epilepsy to Visual Epilepsy
One-Sentence Summary
Perampanel is a selective, non-competitive AMPA receptor antagonist originally used as an antiseizure medication for focal-onset (partial-onset) and primary generalized tonic-clonic seizures in epilepsy. The TxGNN model predicts it may be effective for Visual Epilepsy, a rare reflex epilepsy subtype triggered by visual/photic stimuli, with 3 clinical trials and 19 publications currently available in the evidence pack — but none of these studies were specifically designed for this subtype.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Epilepsy (focal-onset seizures ± secondary generalization; adjunctive treatment of generalized tonic-clonic seizures) — per literature evidence in this pack |
| Predicted New Indication | Visual Epilepsy |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 (mechanistic/preclinical-level; no subtype-specific clinical study) |
| Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
A formal DrugBank-sourced mechanism-of-action record is not available in this evidence pack (data gap). However, multiple literature sources collected for this candidate consistently and independently describe Perampanel as a selective, non-competitive antagonist of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, which mediate glutamate-driven postsynaptic excitation in the central nervous system. This mechanism underlies its broad-spectrum anticonvulsant activity across multiple seizure types.
The original indication (epilepsy with focal-onset and generalized tonic-clonic seizures) and the predicted new indication (visual epilepsy, a photosensitive/visually-induced reflex epilepsy subtype) share the same underlying disease category. Visual epilepsy is characterized by cortical hyperexcitability provoked by visual/photic stimuli — the so-called photoparoxysmal response — which, like other seizure types, is thought to involve excessive AMPA-receptor-mediated glutamatergic transmission.
Mechanistically, an AMPA antagonist that already suppresses cortical hyperexcitability in generalized and focal epilepsy could plausibly dampen the specific visual-trigger pathway as well. This is a reasonable extrapolation from known pharmacology, but it remains a research hypothesis rather than a demonstrated clinical effect, since no trial or publication in this evidence pack directly studies perampanel in patients with visual/photosensitive reflex epilepsy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03780907 | Phase 2 | Completed | 18 | Tolerability, safety and PK of E2007 (perampanel) in patients with refractory partial/generalized seizures; general AED population, not visual-epilepsy specific |
| NCT02900755 | Phase 4 | Completed | 30 | Effects of perampanel on cognition and EEG in epilepsy patients; general population study |
| NCT03653741 | Phase 4 | Completed | 12 | Effects of perampanel on neurophysiology tests (EEG, SEP, BAEP, VEP) in healthy adults; small sample, not disease-specific |
All three trials are graded C (low relevance) — they assess perampanel in general epilepsy or healthy populations, not specifically in visual/photosensitive reflex epilepsy.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36878742 | 2023 | Systematic Review | Brain & Development | Efficacy, tolerability, safety of perampanel in children/adolescents with epilepsy |
| 36206645 | 2022 | Systematic Review/Meta-analysis | Seizure | Efficacy and safety of perampanel across RCTs in epilepsy |
| 29898971 | 2018 | Practice Guideline | Neurology | AAN/AES guideline update on new-onset epilepsy treatment, including perampanel |
| 36150304 | 2022 | Review (trial + real-world evidence) | Epilepsy & Behavior | Perampanel monotherapy for focal/generalized tonic-clonic seizures |
| 24559052 | 2014 | Review | Expert Opin Drug Discov | Discovery and development of perampanel as a first-in-class AMPA antagonist |
| 37378757 | 2023 | Systematic Review/Network Meta-analysis | J Neurol | ASM comparison for idiopathic generalized epilepsies |
| 26111428 | 2015 | Review | Expert Opin Drug Metab Toxicol | Pharmacokinetic/pharmacodynamic evaluation of perampanel |
| 25878177 | 2015 | Post-hoc analysis (Phase 3) | Neurology | Perampanel efficacy/tolerability with enzyme-inducing AEDs |
| 41043235 | 2025 | Prospective multicenter study | Epilepsy & Behavior | Perampanel effects on seizures and sleep quality |
| 37292124 | 2023 | Real-world observational | Front Neurol | Perampanel monotherapy in newly diagnosed pediatric focal epilepsy |
Note: All 19 publications in this evidence pack address perampanel in general epilepsy populations. None specifically studies visual/photosensitive reflex epilepsy.
EU Market Information
No marketing authorizations are recorded for this candidate in the current dataset (market status: Not Marketed; 0 authorizations on file).
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Current evidence is limited to L4 (mechanistic/preclinical-level rationale). All 3 registered clinical trials are graded “C” relevance — they study perampanel in general epilepsy populations, not the visual/photosensitive reflex epilepsy subtype — and none of the 19 publications directly addresses this indication.
To proceed, the following is needed:
- A dedicated clinical study (or at minimum case series) of perampanel in visual/photosensitive reflex epilepsy patients
- TFDA/regulatory safety labeling data (currently blocking data gap — key warnings and contraindications unavailable)
- Confirmed DrugBank-sourced MOA record (currently a data gap)
- Confirmation of original indication and regulatory/marketing status (0 authorizations currently on file)
Note: Within this same drug’s broader prediction set, status epilepticus (rank 10, TxGNN score 99.77%) shows substantially stronger evidence — evidence level L2, decision stage S2 (“Proceed with Guardrails”), supported by a completed systematic review, multiple cohort studies, and an active Phase 2 RCT (NCT06401707) — and may warrant prioritization as a more promising repurposing candidate for this drug.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.