Valsartan
| Evidence Level: L4 | Predicted Indications: 7 |
Table of Contents
Valsartan: From Hypertension to Malignant Renovascular Hypertension
One-Sentence Summary
Valsartan is an angiotensin II receptor blocker originally used to treat hypertension. The TxGNN model predicts it may be effective for malignant renovascular hypertension, but there are 0 clinical trials and only 1 publication (a preclinical animal study) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertensive disorder / hypertension |
| Predicted New Indication | Malignant renovascular hypertension |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (all licenses cancelled) |
| Number of NDAs | 12 (1 NDA and 11 ANDAs, all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, valsartan is an angiotensin II type 1 (AT1) receptor blocker. Its efficacy in hypertension is established, and mechanistically it may be applicable to malignant renovascular hypertension, in which the renin-angiotensin system plays a central role.
The predicted indication is very close to the approved one. Malignant renovascular hypertension is a severe, renin-driven form of hypertension. The one supporting paper (PMID 11560862, 2001) reports that AT1 receptor blockade prevented lethal malignant hypertension in an animal model, partly independent of blood pressure lowering. This evidence is indirect, because the study was not specific to valsartan and was not conducted in humans. Because the indication is so close to hypertension, it offers little repurposing novelty.
Other predictions in the same list are weaker. Malignant hypertensive renal disease has only an avosentan paper (a different drug). The pulmonary hypertension predictions rest mostly on animal and cell studies, or on sacubitril/valsartan, a combination product. Braddock syndrome and pulmonary hypertension with unclear multifactorial mechanism have no supporting evidence beyond the model score.
Clinical Trial Evidence
Currently no related clinical trials are registered for the lead predicted indication, malignant renovascular hypertension.
For the sixth-ranked prediction, chronic pulmonary heart disease, one trial matched, but it is not relevant:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02966665 | Phase 1 | Recruiting | 420 | Exercise rehabilitation and vascular function in hypertension; does not test valsartan for this indication |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 11560862 | 2001 | Preclinical (animal) | Circulation | AT1 receptor blockade prevented lethal malignant hypertension, related to reduced kidney inflammation |
Literature for other predicted indications is mostly indirect (examples):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 24368192 | 2014 | Preclinical (avosentan, a different drug) | Pharmacological Research | Endothelin antagonist protective in hypertensive nephropathy (malignant hypertensive renal disease) |
| 32552157 | 2020 | Preclinical (animal) | J Am Heart Assoc | Sacubitril/valsartan attenuated right ventricular remodeling in pulmonary hypertension |
| 22377232 | 2012 | Preclinical (animal) | Diabetes Res Clin Pract | Valsartan inhibited the HIF-1α pathway and reduced renal fibrosis in diabetic rats |
| 39210725 | 2024 | Post hoc analysis of RCTs | JAMA Cardiology | Sacubitril/valsartan and all-cause hospitalizations in heart failure (not cor pulmonale) |
US Market Information
All 12 US authorizations are listed as cancelled, and none carries approved indication text in the data compiled for this report. Five examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA021283 | Diovan (Novartis) | Tablet | Not available |
| ANDA203311 | Valsartan (Proficient Rx) | Film-coated tablet | Not available |
| ANDA204821 | Valsartan (A-S Medication Solutions) | Tablet | Not available |
| ANDA214102 | Valsartan (ANI Pharmaceuticals) | Solution | Not available |
| ANDA090866 | Valsartan (Mylan) | Film-coated tablet | Not available |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for safety information.
- Knowledge-graph contraindication signals (not label text): liver failure, liver disease, pancreatitis, gallbladder disease, angioedema (including hereditary and ACE/RAAS-blocker-induced forms), systemic lupus erythematosus, diabetes mellitus and diabetic ketoacidosis, neutropenia/agranulocytosis, hypotensive disorder, anuria, impaired renal function, renal artery obstruction, gout, hyperparathyroidism, hypercalcemia, and potassium deficiency. These come from a network database and must be confirmed against the label.
- Drug Interactions (100 recorded; examples):
- Major: potassium chloride and potassium bicarbonate (risk of hyperkalemia).
- Moderate: hydrocortisone, eluxadoline, exenatide, polyethylene glycol with electrolytes, and many insulin products.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (99.97%), but the evidence is only one preclinical animal paper and no clinical trials (Evidence Level L4). The new indication is also nearly identical to the original hypertension indication, so it adds little novelty. All US licenses are cancelled, and safety label data is missing.
To proceed, the following is needed:
- The FDA package insert (warnings and contraindications), which is a blocking gap for safety screening
- Detailed mechanism of action data from DrugBank
- Clinical data specific to valsartan in malignant or renovascular hypertension
- Clarification of why all US licenses are marked cancelled, and of the current market status
- A decision on whether this near-duplicate indication is worth pursuing, or whether to prioritize a more distinct candidate
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.