Benralizumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Benralizumab
- Benralizumab: From Eosinophilic Pneumonia to Thrombocytopenia Due to Immune Destruction
Benralizumab: From Eosinophilic Pneumonia to Thrombocytopenia Due to Immune Destruction
One-Sentence Summary
Benralizumab is an anti-IL-5 receptor alpha antibody, originally associated with eosinophilic pneumonia and pulmonary eosinophilia, and marketed for severe eosinophilic asthma. The TxGNN model predicts it may be effective for thrombocytopenia due to immune destruction, but this is a computational prediction only, with 0 clinical trials and 0 publications supporting it. Among the other top-ranked predictions, dermatitis has the most supporting evidence (3 clinical trials and 19 publications), and it is discussed below as the most developed alternative direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Eosinophilic pneumonia; pulmonary eosinophilia (the approved indication text in the Singapore licences is blank) |
| Predicted New Indication | Thrombocytopenia due to immune destruction |
| TxGNN Prediction Score | 99.34% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. From known information, benralizumab is a monoclonal antibody against the IL-5 receptor alpha subunit (IL5RA). It depletes eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). It is approved in the US for severe eosinophilic asthma and, since September 2024, for eosinophilic granulomatosis with polyangiitis (EGPA).
The link between eosinophil-driven lung disease and immune thrombocytopenia is weak. Immune thrombocytopenia is caused by autoantibody-mediated platelet destruction, and no mechanistic route from eosinophil or basophil depletion to this condition is established. The high score is likely a graph-based propagation from related immune-mediated disease nodes and should not be read as evidence of efficacy.
Dermatitis (rank 2, score 99.16%) is the more plausible direction. Eosinophils, basophils and type 2 innate lymphoid cells contribute to type 2 skin inflammation, so depleting them has a reasonable rationale. However, the larger Phase 2 trial was terminated, and a published report describes a lack of effect (see below).
Clinical Trial Evidence
No clinical trials are registered for the top predicted indication, thrombocytopenia due to immune destruction. Currently no related clinical trials registered.
For reference, trials for the second-ranked prediction (dermatitis) are:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04605094 | Phase 2 | Terminated | 194 | HILLIER study: randomized, double-blind, placebo-controlled, 16 weeks plus 36-week extension, in moderate-to-severe atopic dermatitis despite topical treatment. Terminated early. |
| NCT03563066 | Phase 2 | Completed | 20 | Effects of benralizumab on eosinophils, basophils and innate lymphoid type 2 cells in atopic dermatitis. Small mechanistic study, no results in the data compiled. |
| NCT06734884 | Phase 2 | Not yet recruiting | 96 | Anti-IL-5R therapy in DRESS (drug reaction with eosinophilia and systemic symptoms). Planned start January 2027, so no evidence yet. |
Literature Evidence
No literature is available for the top predicted indication. Currently no related literature available.
For reference, the most relevant publications for dermatitis are:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37178404 | 2023 | Phase 2 RCT report | J Eur Acad Dermatol Venereol | HILLIER trial: reported lack of effect of benralizumab on signs and symptoms of moderate-to-severe atopic dermatitis. |
| 35987486 | 2022 | Review | J Allergy Clin Immunol Pract | Safety of biologics, including benralizumab, for atopic diseases during pregnancy. |
| 34642091 | 2021 | Review | Ann Allergy Asthma Immunol | Guidance on choosing biologics for asthma, atopic dermatitis and related conditions. |
| 39600395 | 2024 | Review | Allergologie Select | Update on biologics for atopic diseases, urticaria and angioedema, with safety focus on hypersensitivity. |
| 36411004 | 2023 | Review | Immunol Allergy Clin North Am | Biologics for allergic disease during pregnancy and lactation. |
| 31690400 | 2019 | Review | Allergy Asthma Proc | Immunobiologics, including anti-IL-5 agents, for severe asthma, atopic dermatitis and chronic urticaria. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16043P | FASENRA solution for injection 30 mg/mL (autoinjector pen) | Injection, solution | Not stated in the data compiled |
| SIN15683P | FASENRA solution for injection 30 mg/mL (pre-filled syringe) | Injection, solution | Not stated in the data compiled |
Safety Considerations
Please refer to the package insert for safety information.
No drug-drug interaction signals were identified in the data compiled; the single pharmacology record only confirms that the target is IL5RA. No knowledge-graph contraindications were identified.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication, thrombocytopenia due to immune destruction, has no registered trials or literature and no plausible mechanistic link to IL-5R-mediated eosinophil depletion. The same applies to the related autoimmune cytopenia predictions (autoimmune thrombocytopenic, Evans syndrome). The only prediction with trial activity, dermatitis, has an informative negative result: the HILLIER trial was terminated and reported no effect in atopic dermatitis.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA, which are required before any safety screening
- Mechanism of action data from DrugBank
- A mechanistic or clinical rationale connecting IL-5Rα blockade to immune thrombocytopenia, such as case reports or preclinical data
- If dermatitis is pursued instead, the reason for termination of NCT04605094, the results of NCT03563066, and the outcome of the DRESS trial (NCT06734884) once it starts
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.