Cyclosporine
| Evidence Level: L4 | Predicted Indications: 7 |
Table of Contents
- Cyclosporine
- Cyclosporine: From Immunosuppression to Chronic Granulomatous Disease (Autosomal Recessive)
Cyclosporine: From Immunosuppression to Chronic Granulomatous Disease (Autosomal Recessive)
One-Sentence Summary
Cyclosporine is a calcineurin inhibitor used to suppress immune responses, including graft-versus-host disease (GVHD) prophylaxis after stem cell transplant. The TxGNN model predicts it may be relevant to autosomal recessive chronic granulomatous disease (CGD), but only 1 clinical trial (indirect) and 1 publication (indirect) exist, so the evidence is weak. The link is supportive (transplant care), not disease-modifying.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the source data (approved indication text is empty for all licenses) |
| Predicted New Indication | Granulomatous disease, chronic, autosomal recessive |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, cyclosporine is a calcineurin inhibitor used for GVHD prophylaxis in transplant settings.
Allogeneic hematopoietic stem cell transplant (HSCT) can cure CGD. In that setting, cyclosporine helps the graft take and prevents GVHD. It does not treat the underlying phagocyte defect of CGD, so its role would be as part of the transplant regimen.
It also cannot be confirmed that cyclosporine was part of the regimen in the cited CGD transplant study. The high TxGNN score most likely reflects the drug’s association with transplant medicine, not direct therapeutic activity in CGD.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01917708 | Phase 1 | Completed | 10 | Single-arm study of abatacept added to cyclosporine and mycophenolate mofetil as GVHD prophylaxis in children receiving unrelated donor HSCT for non-malignant diseases. Cyclosporine is background therapy, not the tested drug, and the cohort is not CGD-specific (relevance grade C). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22078471 | 2012 | Retrospective cohort | J Allergy Clin Immunol | Reports excellent survival after sibling or unrelated donor HSCT in CGD. The abstract does not specify cyclosporine use. |
US Market Information
Of the 20 licenses, the first five records are shown. One (ANDA065110) appears twice and is listed once. Approved indication text is empty in the source data.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA050790 | Restasis MultiDose | Emulsion | Allergan, Inc. |
| ANDA065110 | Cyclosporine | Capsule, liquid filled | Teva Pharmaceuticals USA, Inc. |
| ANDA065040 | Cyclosporine | Capsule, gelatin coated | Apotex Corp. |
| ANDA065003 | Gengraf | Capsule | AbbVie Inc. |
Available forms include oral capsules, an ophthalmic emulsion, and solution or drops.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting evidence is one Phase 1 trial where cyclosporine is background therapy and one retrospective HSCT cohort. Neither tests cyclosporine in CGD. Cyclosporine’s plausible role is supportive transplant immunosuppression, not treatment of CGD itself, and the candidate stays at the research-question stage (S1).
To proceed, the following is needed:
- Confirm whether cyclosporine was part of the conditioning or GVHD prophylaxis regimens in CGD transplant studies, and whether outcomes differ with it
- Package insert warnings and contraindications (currently a blocking gap)
- Mechanism of action data from DrugBank
- Consider prioritizing other predicted indications with more literature. Brain aneurysm (L3) has small studies of cyclosporine A in subarachnoid hemorrhage, and the other five predictions have little or no evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.