Ubrogepant
| Evidence Level: L3 | Predicted Indications: 3 |
Table of Contents
Ubrogepant: From Migraine to Migraine with Brainstem Aura
One-Sentence Summary
Ubrogepant is an oral CGRP receptor antagonist (gepant), originally used for the acute treatment of migraine with or without aura. The TxGNN model predicts it may be effective for migraine with brainstem aura, with no registered clinical trials specific to this subtype and 19 publications on ubrogepant in migraine more broadly, so the evidence for this subtype is indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Migraine (migraine disorder; migraine with or without aura) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L3 |
| US Market Status | Cancelled only (the single NDA is listed as cancelled in the data compiled for this report) |
| Number of NDAs | 1 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, ubrogepant is a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist. Its efficacy in acute migraine with or without aura has been shown in Phase 3 trials.
Migraine with brainstem aura is a subtype of migraine with aura and shares the trigeminovascular, CGRP-mediated pathophysiology. The high TxGNN score is consistent with this overlap. This is effectively an extension within the same disease family rather than true repurposing.
Brainstem aura symptoms (vertigo, dysarthria, diplopia, ataxia) have historically led to cautions or exclusions for vasoconstrictor-based therapies such as triptans. Gepants lack vasoconstrictive activity, which is a plausible safety advantage, but this needs confirmation in this subtype. The pivotal trials were not subtype-specific, so the evidence is indirect.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37979595 | 2023 | RCT (Phase 3) | Lancet | Ubrogepant 100 mg vs placebo for treating migraine attacks during the prodrome (crossover, multicentre, USA) |
| 31800988 | 2019 | RCT | N Engl J Med | Pivotal trial of ubrogepant, an oral CGRP receptor antagonist, for acute migraine treatment |
| 39569702 | 2025 | Clinical trial (safety) | Headache | TANDEM study: safety and tolerability of ubrogepant in people taking atogepant for episodic migraine prevention |
| 31913519 | 2020 | Phase 3 extension | Headache | 52-week long-term safety and tolerability of ubrogepant |
| 33547676 | 2021 | Real-world study | Headache | Real-world efficacy, tolerability and safety in a tertiary headache centre |
| 35790906 | 2022 | Network meta-analysis | J Headache Pain | Relative efficacy of lasmiditan versus rimegepant and ubrogepant for acute migraine |
| 38307667 | 2024 | Review | Handb Clin Neurol | Overview of gepants; second-generation agents ubrogepant and rimegepant are approved for acute migraine |
| 32020557 | 2020 | Review | Drugs | First approval summary: approved in the USA in December 2019 for acute migraine (± aura) in adults |
| 33948091 | 2021 | Narrative review | J Pain Res | ACHIEVE I and II showed superiority to placebo for pain freedom at 2 hours |
| 39262541 | 2024 | Case report | Cureus | Treatment-resistant migraine patient with substantial improvement on ubrogepant |
None of these publications is specific to the brainstem aura subtype.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA211765 | UBRELVY (Allergan, Inc.) | Tablet | Status: cancelled in the data compiled for this report |
Safety Considerations
- Drug Interactions: 76 interactions were recorded. Examples of Major interactions: clarithromycin, cobicistat, lumacaftor. Examples of Moderate interactions: aprepitant, dexamethasone, cimetidine, eliglustat, eluxadoline, miconazole, rolapitant, clotrimazole, ticagrelor, quinine, ivacaftor, zafirlukast.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Ubrogepant has strong Phase 3 evidence in acute migraine with or without aura, and brainstem aura is a closely related subtype with shared pathophysiology. However, no subtype-specific trials exist, so the evidence is indirect (L3). The US market status is listed as cancelled and should be verified.
To proceed, the following is needed:
- Subtype-specific data (post hoc analyses or a dedicated study) in migraine with brainstem aura
- Package insert warnings and contraindications (not yet reviewed)
- Detailed mechanism-of-action data
- Verification of the current US market and NDA status
- A review of the major CYP3A4-related drug interactions for patients on concomitant therapy
Other predictions (not recommended to advance): Atrophoderma vermiculata (score 99.40%) and ulerythema ophryogenesis (score 99.23%) are supported only by the model prediction (L5). No trials or publications were found, and no plausible mechanistic link to CGRP receptor antagonism is evident. Decision: Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.