Adapalene
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Adapalene: From Acne Vulgaris to Elevated Plasma Zinc (Likely Model Artifact)
One-Sentence Summary
Adapalene is a topical retinoid, and acne vulgaris is its established use. The SAHPRA registration records supplied do not state the approved indication. The TxGNN model’s top-ranked prediction is elevated plasma zinc, a laboratory finding rather than a treatable disease, and the input contains 0 clinical trials and 0 publications for it. The high score is most likely a knowledge-graph artifact, so this prediction should not be acted on.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the SAHPRA records provided (acne vulgaris is the established use, per the evidence pack’s rationale) |
| Predicted New Indication | Zinc, elevated plasma |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L5 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the input. Based on general knowledge, adapalene is a selective retinoic acid receptor (RAR-beta/gamma) agonist. It normalises follicular keratinisation and has anti-inflammatory activity in pilosebaceous units. This is the basis of its efficacy in acne vulgaris.
For elevated plasma zinc, no plausible mechanism was identified. It is a laboratory abnormality, not a disease with a therapeutic target, and topical adapalene has minimal systemic exposure. The score of 99.51% therefore appears to reflect a knowledge-graph artifact rather than a real therapeutic signal. The prediction should be treated as a modelling curiosity, not a repurposing lead.
Other Predicted Candidates
The model produced nine further candidates. The table below summarises them; only two (ranks 8 and 9) have any retrieved evidence.
| Rank | Predicted Indication | Score | Evidence Level | Recommendation | Comment |
|---|---|---|---|---|---|
| 2 | Isolated congenital adermatoglyphia | 98.80% | L5 | Hold | Genetic (SMARCAD1); no known retinoid link |
| 3 | Beare-Stevenson cutis gyrata syndrome | 98.78% | L5 | Hold | FGFR2 syndrome; speculative link only |
| 4 | Demodicidosis of sebaceous gland | 95.45% | L5 | Research Question | Plausible via pilosebaceous mechanism; no antiparasitic effect documented |
| 5 | Pyogenic arthritis-pyoderma gangrenosum-acne syndrome | 95.30% | L5 | Research Question | Topical use could at most address the acne lesions |
| 6 | Prolidase deficiency | 89.33% | L5 | Hold | No mechanistic path identified |
| 7 | Drug-induced osteoporosis | 87.21% | L5 | Hold | Systemic retinoids may harm bone; direction of effect uncertain |
| 8 | Seborrheic dermatitis | 86.28% | L4 | Research Question | Plausible mechanism, but all evidence is indirect (acne studies) |
| 9 | Sebaceous gland anomaly | 85.16% | L1 | Proceed with Guardrails | Supported by acne Phase 3 evidence; label-concordant, not a novel signal |
| 10 | Inherited skin tumour | 82.92% | L5 | Hold | Loose chemoprevention rationale; no evidence |
Clinical Trial Evidence
For the top prediction (elevated plasma zinc): currently no related clinical trials registered.
The trials below were retrieved for the two candidates with evidence. All concern acne vulgaris, not the predicted conditions themselves.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00446043 | Phase 3 | Completed | 452 | Long-term (12-month) safety and efficacy of adapalene 0.1%/benzoyl peroxide 2.5% gel in acne vulgaris (rank 9; direct adapalene evidence) |
| NCT02557399 | Phase 4 | Completed | 350 | Duac (clindamycin/benzoyl peroxide) vs adapalene + clindamycin combination in Japanese facial acne (rank 9; contextual only) |
| NCT03076320 | Phase 1/2 | Completed | 82 | Zaxcell vs Effezel (adapalene/benzoyl peroxide) in inflammatory and scarring acne (rank 8; not a seborrheic dermatitis study) |
| NCT06281782 | NA | Unknown | 40 | Platelet-rich plasma plus topical retinoids vs topical retinoids alone in acne (rank 8; wrong disease) |
| NCT05497323 | Phase 1 | Unknown | 284 | Adjuvant combination cream vs adapalene 0.1% cream in mild-to-moderate acne (rank 8; wrong disease) |
No SANCTR or PACTR identifiers were included in the input.
Literature Evidence
For the top prediction: currently no related literature available.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39069843 | 2024 | RCT | Ital J Dermatol Venereol | Adapalene 0.3%/benzoyl peroxide 2.5% gel in Korean acne patients, with histopathological and immunohistochemical assessment |
| 25217865 | 2014 | Animal study | J Dermatol Sci | 0.1% adapalene was effective in a non-inflammatory Kyoto Rhino Rat acne model |
| 36102580 | 2022 | Clinical study | J Cosmet Dermatol | Moisturiser (not adapalene) and facial skin lipidome in seborrhoea; not relevant to adapalene |
| 27504089 | 2016 | Case report | Case Rep Dermatol | Localised late-onset Darier’s disease; not relevant to adapalene |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 46/13.11/0162 | Dapta Cream | Cream (topical) | Not stated in the registration record |
| Reg. No. 51/13.12/0911 | Deriva Co | Gel (topical) | Not stated in the registration record |
Essential Medicines List (EML) status could not be determined from the input.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA. The drug-interaction query returned no records.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction, elevated plasma zinc, is a laboratory finding with no plausible mechanism and no supporting trials or literature (L5). The only strong evidence (rank 9, Phase 3 in acne) is for adapalene’s established acne use, so it is not a repurposing signal.
To proceed, the following is needed:
- SAHPRA Professional Information (warnings and contraindications), which is currently blocking safety screening.
- Mechanism of action data from DrugBank.
- The approved indication text for both SAHPRA registrations, to confirm the original indication.
- If a repurposing question is pursued, prioritise the “Research Question” candidates (demodicidosis, seborrheic dermatitis, and the acne component of PAPA-like syndrome) rather than the top-scoring but implausible ones.
- Review of the “sebaceous gland anomaly” result against the acne label before making any claim.
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.