Icatibant
| Evidence Level: L1 | Predicted Indications: 7 |
Table of Contents
Icatibant: From Hereditary Angioedema Attacks to C1 Inhibitor Deficiency
One-Sentence Summary
Icatibant is a bradykinin B2 receptor antagonist injection. It is marketed in the US, and the Evidence Pack lists no approved-indication text. Its known use is acute attacks of hereditary angioedema (HAE). The TxGNN model predicts it may be effective for C1 inhibitor deficiency, with 21 registered clinical trials (several of them Phase 3) and 20 publications supporting this direction. This prediction very likely overlaps with the drug’s existing indication, so it should not be presented as a true repurposing discovery until the label is checked.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute HAE attacks (from known pharmacology; the Evidence Pack’s indication text is empty) |
| Predicted New Indication | C1 inhibitor deficiency |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 10 (the five listed are generic ANDAs) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. Based on known pharmacology, icatibant selectively blocks the bradykinin B2 receptor.
C1 inhibitor deficiency causes uncontrolled kallikrein activity and excess bradykinin, which drives the swelling attacks. Blocking the B2 receptor targets this pathway directly. Hereditary angioedema types I and II are the classic forms of C1 inhibitor deficiency, so the prediction fits the mechanism well.
The original and predicted indications are therefore probably the same disease area. This is likely an on-label use rather than a new one. The only extension beyond HAE is acquired C1-inhibitor deficiency, which is supported by small retrospective studies, one real-world series of 8 patients, and guidelines.
Clinical Trial Evidence
Most trials below are in HAE (C1 inhibitor deficiency types I/II). Other Phase 2/3 HAE trials in the pack (lanadelumab, C1-INH, BCX7353, KVD900, GNR-038) were left out because they do not test icatibant or their link to icatibant is unconfirmed.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00097695 | Phase 3 | Completed | 84 | Randomized, double-blind, placebo-controlled trial of subcutaneous icatibant in acute cutaneous/abdominal HAE attacks |
| NCT00912093 | Phase 3 | Completed | 98 | Randomized, double-blind, placebo-controlled trial of icatibant efficacy and safety in acute HAE attacks |
| NCT00500656 | Phase 3 | Completed | 85 | Icatibant vs oral tranexamic acid; primary endpoint was time to onset of symptom relief |
| NCT00997204 | Phase 3 | Completed | 151 | Open-label study of safety, local tolerability and efficacy of self-administered icatibant |
| NCT03888755 | Phase 3 | Completed | 8 | Open-label study in Japanese patients with type I/II HAE (efficacy, PK, safety) |
| NCT01386658 | Phase 3 | Completed | 32 | Single-arm study of PK, tolerability and safety of one icatibant dose in children and adolescents with HAE |
| NCT04654351 | Phase 3 | Completed | 2 | Safety, efficacy and PK of icatibant in Japanese children and adolescents; very small sample |
| NCT01457430 | Phase 4 | Completed | 19 | Self-administered icatibant vs treatment in a medical facility; supports real-world usability |
| NCT07290855 | Phase 4 | Completed | 5 | Icatibant injection (Icanticure) in bradykinin-induced angioedema in Taiwan; very small sample |
| NCT01034969 | N/A | Completed | 1761 | Icatibant Outcome Survey (IOS) registry of routine clinical outcomes and long-term safety |
Literature Evidence
The pack contains no RCT publications. The table lists reviews, registry data and observational studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22686628 | 2012 | Real-world observational | Allergy | 8 patients with acquired C1-INH deficiency; 48 moderate-to-severe attacks treated with icatibant 30 mg SC |
| 29757016 | 2018 | Review | Expert Rev Clin Immunol | Icatibant in adolescents and children over 2 years with C1-INH-HAE, based on RCT, open-label and observational data |
| 23420425 | 2013 | Systematic review | Pneumonol Alergol Pol | Compared conestat alfa, human C1-INH and icatibant for acute HAE attacks in adults |
| 33602658 | 2021 | Review | J Investig Allergol Clin Immunol | Current C1-INH-HAE therapy, including kallikrein-kinin system inhibition |
| 34965883 | 2021 | Registry | Allergy Asthma Clin Immunol | Icatibant Outcome Survey data from Spain in HAE type 1/2 |
| 35662289 | 2022 | Registry cohort | Clin Exp Allergy | Icatibant and C1-inhibitor use in laryngeal HAE attacks |
| 30280305 | 2018 | Observational | J Clin Immunol | Icatibant and recombinant C1-INH for HAE attacks during pregnancy |
| 37716525 | 2023 | Retrospective cohort | J Allergy Clin Immunol Pract | Acquired C1-INH deficiency (AAE-C1-INH): diagnosis, course and therapy; no licensed therapy |
| 32753245 | 2020 | Guideline | Rev Med Interne | CREAK recommendations for diagnosis and treatment of acquired C1-INH deficiency |
| 37898409 | 2024 | Review | J Allergy Clin Immunol | Burden of C1-INH deficiency HAE in the Asia-Pacific region |
US Market Information
The source data gives no approved-indication text for these authorizations. All five are generic (ANDA) injectables.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA212446 | SAJAZIR (Cycle Pharmaceuticals) | Injection | Not provided |
| ANDA212081 | Icatibant (Bryant Ranch Prepack) | Injection, solution | Not provided |
| ANDA213773 | Icatibant (Alembic Pharmaceuticals Inc.) | Injection | Not provided |
| ANDA213773 | Icatibant (Alembic Pharmaceuticals Limited) | Injection | Not provided |
| ANDA208317 | Icatibant (Fresenius Kabi USA) | Injection, solution | Not provided |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Three completed Phase 3 randomized trials (NCT00097695, NCT00912093, NCT00500656) plus a large registry support icatibant in HAE, which is C1 inhibitor deficiency. This is probably an existing indication rather than a new one. The acquired form of C1-inhibitor deficiency has only observational and guideline support.
To proceed, the following is needed:
- Check the US label to confirm whether HAE/C1 inhibitor deficiency is already an approved indication, and reclassify the finding as on-label if so.
- Obtain the package insert warnings and contraindications, which are missing and block the safety screening.
- Obtain formal MOA data from DrugBank.
- Review the full records of the unclear trials (NCT02584959, NCT04208412, NCT02870972) to confirm whether icatibant is involved.
- If acquired C1-inhibitor deficiency is the target, a prospective controlled study is needed.
Other predictions (ranks 2–7): serpinopathy with toxic serpin polymerization, pseudo-von Willebrand disease, primary release disorder of platelets, immune-mediated necrotizing myopathy, antisynthetase syndrome and Glanzmann thrombasthenia have no trials or literature. No plausible B2-antagonist mechanism was identified for any of them. The recommendation for all six is Hold, and their scores are likely knowledge-graph artifacts.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.