Darolutamide
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Darolutamide
- Pharmacist Assessment Report
- Darolutamide: From Prostate Cancer to Homozygous Familial Hypercholesterolemia
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Darolutamide: From Prostate Cancer to Homozygous Familial Hypercholesterolemia
One-Sentence Summary
Darolutamide is a non-steroidal androgen receptor antagonist marketed in Canada as NUBEQA. The TxGNN model’s top-ranked prediction is homozygous familial hypercholesterolemia, but no clinical trials and no publications support it. This is a model-only prediction with very weak evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the Canadian license data compiled for this report (darolutamide is an androgen receptor antagonist; its use in prostate cancer is general knowledge, not taken from the data) |
| Predicted New Indication | Homozygous familial hypercholesterolemia |
| TxGNN Prediction Score | 0.9911 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, darolutamide is a non-steroidal androgen receptor antagonist.
Homozygous familial hypercholesterolemia is caused by defects in the LDL receptor pathway. There is no clear mechanistic link between androgen receptor blockade and this pathway. The high TxGNN score (0.9911) reflects a network-based prediction only, with no supporting trials or literature, so it should not be read as evidence of efficacy.
Other top-ranked predictions show the same pattern. Most are low-plausibility or likely TxGNN model (deep learning) artifacts: HIV infection. Two have slightly more context:
- Multiple endocrine neoplasia (rank 2, score 0.9906): Two trials were found, both in androgen-driven (likely prostate) cancer settings, where darolutamide’s mechanism is relevant. The match to MEN syndromes is probably a disease-classification artifact.
Clinical Trial Evidence
Currently no related clinical trials registered for homozygous familial hypercholesterolemia.
For reference, the trials linked to the second-ranked prediction (multiple endocrine neoplasia) are:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07795177 | Phase 2 | Not yet recruiting | 40 | Spatial multi-omics study predicting response to androgen deprivation plus second-generation endocrine agents in metastatic hormone-sensitive prostate cancer. Not relevant to MEN. |
| NCT03878524 | Phase 1 | Terminated | 2 | SMMART PRIME precision-oncology platform study. Terminated after only 2 participants, so no usable efficacy or safety signal. |
Literature Evidence
Currently no related literature available for homozygous familial hypercholesterolemia.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 41669591 | 2026 | Case report | Cureus | A 72-year-old man with BRCA2-mutated metastatic prostate cancer developed SIADH and thrombotic microangiopathy as paraneoplastic syndromes. Does not show that darolutamide treats thrombosis. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02496348 | NUBEQA | Not specified | Not specified |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted/hormonal therapy (androgen receptor antagonist), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The interaction screening completed with 100 interactions recorded. The 20 listed in the data include several Major-level interactions:
- Major: Dexamethasone, Eluxadoline, Rosuvastatin
- Moderate: Clarithromycin, Empagliflozin, Glyburide, Glycerol phenylbutyrate, Metreleptin, Repaglinide, Rifaximin, Simvastatin, Sulfasalazine, Troglitazone, Cobicistat, Deferasirox, Eltrombopag, Lusutrombopag
- Minor: Aprepitant, Cimetidine, Miconazole
The Major interaction with rosuvastatin and the Moderate interaction with simvastatin are particularly relevant for a lipid-disorder indication, since patients would likely be on statins.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for these.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction has no trials or literature behind it and no plausible mechanistic link between androgen receptor antagonism and LDL receptor pathway defects. Evidence is L5 (model prediction only). The statin interactions add a further concern for this indication.
To proceed, the following is needed:
- Mechanism of action data (e.g., from DrugBank) to allow a mechanistic-link analysis
- Health Canada package insert warnings and contraindications, which are required before safety screening
- Approved indication text, dosage form, and manufacturer for the Canadian license
- Preclinical or mechanistic evidence linking androgen receptor signaling to LDL receptor or cholesterol metabolism, before any clinical study is considered
- An assessment of whether the lower-ranked predictions (such as multiple endocrine neoplasia) reflect true biology or classification artifacts
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.