Alpelisib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Alpelisib
- Alpelisib: From Breast Cancer (Indication Text Not Recorded in Local Licences) to Pulmonary Hypertension
Alpelisib: From Breast Cancer (Indication Text Not Recorded in Local Licences) to Pulmonary Hypertension
One-Sentence Summary
Alpelisib is an oral PI3K-alpha inhibitor marketed in Singapore as Piqray. The clinical trials in the data compiled for this report are all in breast or ovarian cancer. The TxGNN model predicts it may be effective for pulmonary hypertension, but there are 0 clinical trials and only 1 publication (a case report of alpelisib-induced lung disease), so this prediction rests almost entirely on the model.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the Singapore licence data (the trials compiled point to HR+/HER2- PIK3CA-mutated advanced breast cancer) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.03% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Alpelisib is known to be a selective PI3K-alpha inhibitor. Its efficacy in PIK3CA-mutated advanced breast cancer was shown in the Phase 3 SOLAR-1 trial (NCT02437318).
PI3K/AKT signalling has been implicated in pulmonary vascular remodelling and smooth muscle proliferation. Inhibiting PI3K-alpha is therefore theoretically plausible for pulmonary hypertension.
However, the only publication linked to this prediction reports alpelisib-induced interstitial lung disease. That is a pulmonary safety signal, not evidence of benefit. The high model score is not backed by clinical data, and the pulmonary toxicity signal argues for caution.
Clinical Trial Evidence
Currently no related clinical trials registered for pulmonary hypertension.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35730191 | 2023 | Case report | J Oncol Pharm Pract | Alpelisib-induced interstitial lung disease in a patient with advanced breast cancer; a safety signal, not efficacy evidence |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15917P | PIQRAY 300MG DAILY DOSE PACK (150mg + 150mg) | Film-coated tablet | Not recorded |
| SIN15918P | PIQRAY 200MG DAILY DOSE PACK | Film-coated tablet | Not recorded |
| SIN15916P | PIQRAY 250MG DAILY DOSE PACK (200mg + 50mg) | Film-coated tablet | Not recorded |
All three licences are held by Novartis Pharma Stein AG and are currently valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (PI3K-alpha inhibitor), 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 | Blood glucose (hyperglycaemia is a recognised effect; a Phase 2 study, NCT04300790, tested metformin for prevention), plus respiratory symptoms given the reported interstitial lung disease |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were found, and the 20 listed in the compiled data are all rated Moderate. Most involve antidiabetic drugs, including acarbose, metformin, pioglitazone, glimepiride, glipizide, alogliptin, and the SGLT2 inhibitors canagliflozin, dapagliflozin, empagliflozin and ertugliflozin. GLP-1 agonists (albiglutide, dulaglutide, exenatide) are also listed. Other interacting drugs include dexamethasone, bupropion, alosetron, dronabinol and fidaxomicin.
- Pulmonary signal: A published case report describes alpelisib-induced interstitial lung disease (PMID 35730191).
Please refer to the package insert for key warnings and contraindications, which were not available in the compiled data.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (99.03%), but there are no clinical trials in pulmonary hypertension. The only linked publication is a case report of drug-induced lung disease, which is a safety concern. The mechanistic link through PI3K/AKT is plausible but unproven.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which block safety screening
- Mechanism of action data from DrugBank
- Preclinical evidence of PI3K-alpha inhibition in pulmonary vascular remodelling models
- An assessment of the interstitial lung disease risk in patients with pulmonary vascular disease
- The approved indication text for the Singapore licences
Other predictions, all on hold: migraine variants, kyphoscoliotic heart disease, leprosy, amyotrophic lateral sclerosis, rheumatoid arthritis, thrombotic disease and multiple endocrine neoplasia. Their evidence is either absent or indirect: reviews on PI3K-driven vascular anomalies for thrombotic disease, and breast and ovarian cancer trials that do not enrol patients with multiple endocrine neoplasia.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.