Fremanezumab
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Fremanezumab: From Migraine to Migraine with Brainstem Aura
One-Sentence Summary
Fremanezumab is a humanized anti-CGRP monoclonal antibody, originally used for migraine prevention. The TxGNN model predicts it may be effective for migraine with brainstem aura, but there are currently 0 registered clinical trials specific to this subtype, and the 20 publications compiled are mostly indirect (chronic migraine, aura in general, or mechanism studies).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Migraine disorder (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Fremanezumab is a humanized monoclonal antibody that binds the CGRP ligand. CGRP signalling is central to trigeminovascular activation in migraine. Detailed mechanism-of-action data were not available in the data compiled for this report, so this description relies on the published literature. Preclinical work shows that fremanezumab selectively inhibits trigeminovascular neurons (PMID 28642283).
Migraine with brainstem aura is a subtype of migraine with aura, so it shares the underlying migraine pathway. This is therefore a subtype extension of an already approved disease area rather than a new one. Several small observational studies and case reports have examined anti-CGRP antibodies in migraine aura and hemiplegic migraine, with encouraging but limited signals.
There are important caveats. One preclinical study (PMID 31127003) found that cortical spreading depression-induced arterial dilatation and plasma protein extravasation were unaffected by fremanezumab, suggesting aura-related mechanisms may not be directly blocked. Whether anti-CGRP antibodies work for aura remains an open question, and no studies specific to brainstem aura were found.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The compiled literature includes no RCTs. Below are the most relevant publications, prioritising those on aura and fremanezumab.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35302681 | 2022 | Cohort (post hoc) | Eur J Neurol | Efficacy and quality-of-life outcomes of fremanezumab in difficult-to-treat migraine, with subgroups with and without aura or similar neurological dysfunction |
| 38091211 | 2024 | Observational cohort (pilot) | Neurol Sci | Pilot study asking whether anti-CGRP antibodies are effective for migraine aura |
| 38332541 | 2024 | Case series | CNS Neurosci Ther | Observational series on the effect of anti-CGRP therapy on migraine aura |
| 41618146 | 2026 | Systematic review | J Headache Pain | Individual-patient analysis of anti-CGRP antibodies in hemiplegic migraine, a rare aura subtype |
| 41589756 | 2026 | Case report | Eur J Neurol | Reduced frequency of prolonged sporadic hemiplegic migraine attacks after fremanezumab |
| 37638190 | 2023 | Cohort | Front Neurol | Real-world 3-month efficacy and tolerability of fremanezumab in chronic migraine |
| 40596876 | 2025 | Cohort | J Headache Pain | Tolerability of switching from erenumab to fremanezumab in chronic migraine |
| 31127003 | 2019 | Preclinical | J Neurosci | Fremanezumab did not affect spreading-depression-induced arterial dilatation or plasma protein extravasation, with implications for CGRP's role in aura |
| 28642283 | 2017 | Preclinical | J Neurosci | Selective inhibition of trigeminovascular neurons by fremanezumab |
| 30725283 | 2019 | Review | Handb Exp Pharmacol | Overview of the role of CGRP in migraine |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15937P | AJOVY solution for injection in pre-filled syringe 225 mg/1.5 mL | Injection, solution | Not stated in the available record |
| SIN16344P | AJOVY solution for injection in pre-filled pen 225 mg/1.5 mL | Injection, solution | Not stated in the available record |
Safety Considerations
- Cerebrovascular risk: A 2026 real-world pharmacoepidemiologic study (PMID 42390441) compared CGRP antibodies with onabotulinumtoxinA for the risk of ischaemic stroke or transient ischaemic attack. This is an area under active study and relevant to patients with vascular risk factors.
- Glaucoma: A 2026 multinational cohort study (PMID 42090640) examined glaucoma risk associated with CGRP inhibitors in migraine.
Please refer to the package insert for the full safety information, including warnings, contraindications and drug interactions.
Conclusion and Next Steps
Decision: Hold
Rationale: Fremanezumab is already marketed in Singapore for migraine, and the prediction is a plausible subtype extension. However, no trials exist for brainstem aura, the available evidence is indirect, observational or preclinical (L4), and one preclinical study suggests aura mechanisms may not be directly blocked. The package insert safety information has also not been reviewed.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, and the approved indication text for the two Singapore licences
- Detailed mechanism-of-action data
- Prospective or registry data on fremanezumab specifically in migraine with brainstem aura (and hemiplegic migraine)
- Review of the cerebrovascular safety data for patients with vascular risk factors
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.