Lasmiditan
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Lasmiditan: From Acute Migraine to Migraine with Brainstem Aura
One-Sentence Summary
Lasmiditan (US brand name Reyvow) is an oral 5-HT1F receptor agonist approved in the US for the acute treatment of migraine with or without aura in adults. The TxGNN model predicts it may also be useful for migraine with brainstem aura, a specific aura subtype. This prediction has 0 registered clinical trials and 18 publications behind it. The publications mostly cover migraine in general, and none tests lasmiditan directly in brainstem aura.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute treatment of migraine with or without aura in adults (taken from the literature, because the US license records contain no indication text) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 2 records (both are NDA211280) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the source record. Based on the literature, lasmiditan is a selective serotonin 5-HT1F receptor agonist and the first and only FDA-approved drug of this type. Unlike triptans, it acts on the trigeminovascular pathway without causing vasoconstriction. This mechanistic description comes from the cited publications and general knowledge, not from structured drug data.
The original indication (acute migraine with or without aura) already covers migraine with aura. Migraine with brainstem aura is a rare aura subtype whose pathophysiology is not fully understood. A recent review proposes that spreading depolarization probably causes aura and may also trigger trigeminal sensory activation, which underlies the headache. Vasodilation is considered only a secondary feature. Because lasmiditan works on the neuronal pain pathway and not through blood vessels, it is plausible that it could relieve the headache phase in this subtype.
This link is only a hypothesis. No study in the evidence set gives lasmiditan to patients with brainstem aura. The only brainstem aura paper is a case report that does not involve lasmiditan.
Clinical Trial Evidence
Currently no related clinical trials registered.
The pivotal Phase 3 trials cited in the literature (see below) enrolled patients with migraine with or without aura in general. They were not designed to test brainstem aura.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32857291 | 2020 | Systematic review / Meta-analysis of RCTs | CNS Drugs | Lasmiditan is the first and only FDA-approved 5-HT1F agonist for acute migraine with or without aura |
| 31132795 | 2019 | Phase 3 RCT | Brain | Randomized, placebo-controlled study of lasmiditan in migraine with and without aura, including patients with cardiovascular history |
| 36138260 | 2022 | RCT subgroup analysis | Adv Ther | Efficacy of lasmiditan across patient and migraine characteristics in Japanese patients (MONONOFU trial) |
| 33990951 | 2021 | Phase 2 RCT | Headache | Efficacy and safety of lasmiditan in Japanese adults with migraine |
| 22459549 | 2012 | Phase 2 RCT | Lancet Neurol | Oral lasmiditan, a 5-HT1F agonist without vasoconstrictor activity, was tested for acute migraine in a dose-ranging study |
| 32783644 | 2020 | Post hoc analysis of 2 Phase 3 RCTs | Curr Med Res Opin | Assessed whether common migraine comorbidities affect lasmiditan efficacy and safety |
| 35790906 | 2022 | Network meta-analysis | J Headache Pain | Indirect comparison of lasmiditan with rimegepant and ubrogepant for onset of efficacy in acute migraine |
| 31749059 | 2019 | Review (approval summary) | Drugs | FDA approval in October 2019 was based on two positive pivotal Phase 3 trials |
| 33907459 | 2021 | Case report / Review | J Pain Res | Describes migraine with brainstem aura accompanied by disorders of consciousness. Lasmiditan is not involved |
| 35027572 | 2022 | Review | Nat Rev Dis Primers | Migraine overview. Spreading depolarization is the probable cause of aura, and vasodilation is only secondary |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA211280 | Reyvow (Eli Lilly and Company) | Tablet (oral) | Acute treatment of migraine with or without aura in adults (per literature; the license record has no indication text) |
The source lists two license entries, both identical (NDA211280, Reyvow, tablet), so they are shown once here.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, and lasmiditan is already marketed for migraine with or without aura. However, no trial or study tests it in migraine with brainstem aura, so the evidence for this specific subtype is at the mechanism-plausibility level (L4). Safety data and mechanism data are also missing from the record. This is best treated as a research question, not a development candidate. The other two predicted indications (atrophoderma vermiculata and ulerythema ophryogenes, both L5) have no plausible mechanistic link to lasmiditan and are not recommended for follow-up.
To proceed, the following is needed:
- Package insert warnings and contraindications, which are currently missing and block safety screening
- Structured mechanism of action data (for example from DrugBank)
- Subgroup analyses from the existing Phase 3 trials, or new case series, showing lasmiditan’s effect specifically in patients with brainstem aura
- A safety review for this subtype, given the neurological symptoms of brainstem aura and lasmiditan’s central nervous system effects
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.