Lasmiditan
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Lasmiditan: From Migraine (Acute Treatment) to Migraine with Brainstem Aura
One-Sentence Summary
Lasmiditan (DrugBank DB11732) is a selective 5-HT1F receptor agonist whose published, literature-confirmed indication is acute treatment of migraine, with or without aura, in adults. The TxGNN model predicts it may also be effective specifically for migraine with brainstem aura, a rare migraine subtype, with 0 clinical trials and 18 publications currently identified as supporting context — though none of the trials or publications are subtype-specific to lasmiditan in this population.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute treatment of migraine, with or without aura (per literature evidence, e.g. PMID 31749059) — not captured in the regulatory license database (see Market Status note below) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L1 |
| US Market Status | Not Marketed (per regulatory database; this appears inconsistent with the literature-reported 2019 FDA approval of lasmiditan (REYVOW) — flagged as a data quality gap, not resolved here) |
| Number of NDAs | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available from DrugBank in this evidence pack (flagged as a blocking data gap, DG002). Based on the literature evidence collected, lasmiditan is a highly selective serotonin 5-HT1F receptor agonist. It acts on the trigeminovascular system to suppress CGRP release and pain transmission, and — unlike triptans (5-HT1B/1D agonists) — it lacks meaningful 5-HT1B-mediated vasoconstrictor activity.
Migraine with brainstem aura (formerly “basilar-type migraine”) has traditionally been treated cautiously with triptans because of theoretical vasoconstriction risk in the vertebrobasilar circulation. Lasmiditan’s non-vasoconstrictive mechanism is therefore mechanistically plausible for this subtype, since it would not carry the same theoretical contraindication.
However, this is an extrapolation rather than a demonstrated effect: the pivotal Phase 2/3 RCTs (e.g. PMID 31132795, 22459549, 33990951) and subsequent reviews/meta-analyses were conducted in general migraine populations with or without aura, and none of the 18 identified publications report outcomes specific to the brainstem-aura subtype in lasmiditan-treated patients. The prediction rests on plausible mechanistic reasoning, not on direct subtype-specific evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31132795 | 2019 | Phase 3 RCT | Brain | Randomized, placebo-controlled Phase 3 study confirming efficacy of oral lasmiditan for acute migraine, including a generalizable population with cardiovascular history. |
| 22459549 | 2012 | Phase 2 RCT | The Lancet. Neurology | Dose-ranging, placebo-controlled Phase 2 study establishing efficacy and tolerability of oral lasmiditan for acute migraine treatment. |
| 33990951 | 2021 | Phase 2 RCT | Headache | Placebo-controlled Phase 2 study confirming efficacy and safety of lasmiditan in Japanese migraine patients. |
| 32857291 | 2020 | Systematic Review/Meta-analysis of RCTs | CNS Drugs | Confirms FDA-approved oral lasmiditan (100/200 mg) as the first 5-HT1F receptor agonist for acute migraine with or without aura. |
| 35790906 | 2022 | Network Meta-analysis | The Journal of Headache and Pain | Indirect comparison of lasmiditan versus rimegepant and ubrogepant for acute oral migraine treatment, in the absence of head-to-head trials. |
| 33633424 | 2020 | Review | Psychopharmacology Bulletin | Reviews lasmiditan’s efficacy and safety profile for migraine treatment with or without aura. |
| 31749059 | 2019 | Review (regulatory approval profile) | Drugs | Summarizes the October 2019 FDA approval of lasmiditan 50/100 mg tablets for acute migraine with or without aura, based on two pivotal Phase 3 trials. |
| 36138260 | 2022 | Post-hoc subgroup analysis | Advances in Therapy | Secondary analysis of the MONONOFU trial evaluating lasmiditan efficacy across patient and migraine characteristics in Japanese patients. |
| 32783644 | 2020 | Post-hoc analysis | Current Medical Research and Opinion | Post-hoc analysis of two Phase 3 RCTs showing lasmiditan efficacy/safety are maintained in patients with common migraine comorbidities. |
| 33907459 | 2021 | Case report/clinical discussion | Journal of Pain Research | Describes clinical characteristics of migraine with brainstem aura accompanied by disorders of consciousness — relevant to the target disease subtype but not lasmiditan-specific. |
US Market Information
No licenses/authorizations are recorded in the regulatory database (total_licenses: 0). This is inconsistent with literature evidence indicating lasmiditan (brand name REYVOW) received FDA approval in October 2019 — flagged for data reconciliation rather than assumed.
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and DDI data are not available in the current evidence pack — flagged as a blocking data gap, DG001.)
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Lasmiditan’s non-vasoconstrictive 5-HT1F mechanism provides a plausible rationale for use in migraine with brainstem aura, and its efficacy for general migraine (with/without aura) is well supported by Phase 2/3 RCTs and meta-analyses. However, no clinical trial or publication in this evidence pack directly studies lasmiditan in the brainstem-aura subtype, so the prediction remains mechanistic extrapolation.
To proceed, the following is needed:
- TFDA/FDA label warnings and contraindications (currently blocking — DG001)
- Confirmed DrugBank mechanism-of-action data (currently high-severity gap — DG002)
- Reconciliation of the “not marketed / 0 licenses” regulatory status against the literature-reported FDA approval
- A subtype-specific case series or trial in migraine with brainstem aura patients before any clinical use is considered
- Note: two other TxGNN-predicted indications for this drug (atrophoderma vermiculata, ulerythema ophryogenesis) were screened and assessed as likely knowledge-graph false positives (L5, no supporting evidence) — Hold, not pursued further.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.