Formoterol
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Formoterol: From Asthma and COPD to Respiratory Malformation
One-Sentence Summary
Formoterol is a long-acting beta2-agonist bronchodilator, used in fixed-dose inhaler combinations for asthma and chronic obstructive pulmonary disease (COPD). The TxGNN model’s top-ranked prediction is respiratory malformation, but 0 clinical trials and no relevant publications support it, so it looks like a knowledge-graph artifact. The better-supported predictions, obstructive lung disease and asthma, are already approved uses and do not count as repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Asthma and COPD (maintenance treatment, in combination with an inhaled corticosteroid and/or long-acting muscarinic antagonist) |
| Predicted New Indication | Respiratory malformation |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L5 |
| EU Market Status | Cancelled only (all licences cancelled) |
| Number of Authorizations | 10 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, formoterol is a long-acting beta2-agonist that relaxes airway smooth muscle through cAMP-mediated signalling. Its efficacy in asthma and COPD is established.
The link to respiratory malformation is weak. A bronchodilator can ease airflow obstruction, but it is not expected to correct structural malformations. None of the 9 publications retrieved for this prediction address congenital respiratory malformations. They cover COPD, asthma, Down syndrome cognition, post-COVID small airway disease and allergic bronchopulmonary mycosis. The high score most likely reflects network proximity to formoterol’s established bronchodilator use rather than a genuine new-indication signal.
Other predictions for this drug:
- Obstructive lung disease (score 99.90%, evidence L1) and asthma (score 99.74%, evidence L1) are on-label uses, supported by large Phase 3 programmes.
- Bronchitis (score 99.92%) is supported only indirectly, through COPD trials.
- Rienhoff syndrome (score 99.90%) and asthma-related traits, susceptibility to (score 99.50%) have no trials or literature behind them.
Clinical Trial Evidence
Currently no related clinical trials registered for respiratory malformation.
For context, the most relevant trials under the closely related predicted indications are:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04320342 | Phase 3 | Completed | 3406 | Beclomethasone/formoterol/glycopyrronium triple therapy vs dual therapy over 52 weeks in COPD (obstructive lung disease) |
| NCT03162055 | Phase 3 | Completed | 1119 | Glycopyrronium/formoterol vs umeclidinium/vilanterol over 24 weeks in COPD (obstructive lung disease) |
| NCT00064415 | Phase 3 | Completed | 799 | 12-month chronic safety study of arformoterol (a formoterol enantiomer) in COPD (bronchitis) |
| NCT00250679 | Phase 3 | Completed | 443 | 6-month long-term safety study of arformoterol in COPD (bronchitis) |
| NCT00381485 | Phase 3 | Completed | 834 | 12-week mometasone/formoterol vs mometasone alone in persistent asthma |
| NCT00651651 | Phase 3 | Completed | 450 | 12-week budesonide/formoterol vs its monocomponents and placebo in asthma |
| NCT01167010 | Phase 3 | Completed | 552 | Non-inferiority comparison of formoterol/budesonide inhalation products in asthma |
| NCT00624754 | Phase 2 | Completed | 32 | Budesonide/formoterol in bronchiolitis obliterans after stem cell transplant (bronchitis) |
These trials concern approved indications, not respiratory malformation.
Literature Evidence
Literature retrieved for respiratory malformation is not relevant to the predicted condition:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40840693 | 2026 | Systematic review / meta-analysis | J Am Pharm Assoc | Budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol in COPD |
| 35115339 | 2022 | RCT | Eur Respir J | Repeated-dose budesonide/formoterol vs salbutamol in adult asthma: bronchodilator, cardiovascular and adverse effects |
| 22541245 | 2012 | RCT | J Allergy Clin Immunol | Long-term safety of budesonide/formoterol pMDI in African American asthmatic patients |
| 20528601 | 2010 | Review | J Asthma | Budesonide/formoterol pMDI in persistent asthma |
| 35034195 | 2022 | Physiological study | Eur J Appl Physiol | Compensatory responses to increased mechanical load in COPD during sleep |
None of these address congenital respiratory malformations.
EU Market Information
All 10 EU authorizations are cancelled. No licence is currently valid.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| EMEA/H/C/003890 | BiResp Spiromax | Not specified | Asthma (adults and adolescents 12+) and COPD (adults 18+) with a budesonide/formoterol combination… |
| EMEA/H/C/002348 | DuoResp Spiromax | Not specified | Asthma (adults and adolescents 12+) and COPD (adults 18+), regular treatment where a combination is appropriate… |
| EMEA/H/C/004882 | GoResp Digihaler (previously Budesonide/Formoterol Teva Pharma B.V.) | Not specified | Asthma and COPD in adults 18 years and older, regular treatment where a combination is appropriate… |
| EMEA/H/C/004983 | Trixeo Aerosphere | Not specified | Maintenance treatment of moderate to severe COPD in adults not adequately treated by ICS/LABA or LABA/LAMA… |
| EMEA/H/C/004257 | Trimbow | Not specified | Maintenance treatment of asthma and COPD in adults not adequately controlled on LABA plus ICS… |
Safety Considerations
- Disease-level cautions from the knowledge graph (these are model-derived contraindication edges, not label text): hypertension, long QT syndrome, epilepsy, liver disease, gallbladder disease, herpes simplex keratitis, measles, and several pituitary hormone deficiency conditions.
- Drug Interactions: 463 interactions were identified. Examples:
- Moderate: acarbose, famotidine, clarithromycin, cisapride, dolasetron, ephedrine, isometheptene, and the antidiabetic agents albiglutide, alogliptin, canagliflozin, chlorpropamide, dapagliflozin, dulaglutide and empagliflozin.
- Minor: corticosteroids (beclomethasone, betamethasone, budesonide, dexamethasone).
Please refer to the SmPC for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The respiratory malformation prediction rests only on a model score. There are no trials or relevant publications, and a beta2-agonist is not expected to correct structural malformations. The well-supported predictions (obstructive lung disease, asthma) are existing approved uses, not repurposing, and all EU licences are currently cancelled.
To proceed, the following is needed:
- Mechanistic evidence for any role of beta2-agonism in respiratory malformation, along with detailed mechanism of action data
- Warnings and contraindications from the SmPC, which are currently unavailable
- Confirmation of current product availability and formulation, given that all EU licences are cancelled
- If an on-label route is pursued, review of the asthma and obstructive lung disease predictions, which could be considered for “Proceed with Guardrails”
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.