What Is Alpelisib (Piqray, Pimreva)? FDA Approval, Turkish Authorization and Reimbursement
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A New Option for PIK3CA-Mutated Breast Cancer: Alpelisib
The PIK3CA mutation, present in around 40% of patients with hormone receptor (HR)-positive, HER2-negative breast cancer, is a major mechanism behind progression and treatment resistance. Alpelisib (Piqray® / Pimreva®) entered oncology practice as the first PI3K inhibitor targeting this mutation to block signaling pathways.
Drug Profile
- FDA Approved: Yes (first approval: 24 May 2019)
- Active Ingredient: Alpelisib
- Brand Name: Piqray (United States), Pimreva (Turkey)
- Administration: Tablet
- Class: Signal transduction inhibitor, PI3K inhibitor
- Category: Targeted agent
- Manufacturer: Novartis
- Distribution in Turkey: Farmanova Sağlık Hiz.
- Approved Cancer: Breast cancer, PIK3CA-related overgrowth spectrum
- Authorization: Authorized in Turkey on 25.12.2021.
- Reimbursement: Currently, Turkey’s Social Security Institution (SGK) does not reimburse it.
- Price: The selling price for 56 tablets of 150 mg, 28 tablets of 200 mg or 56 tablets of 200+50 mg is 123384.33 ₺.
- Cost per Cycle: At the recommended daily dose of 300 mg (2 tablets of 150 mg), one pack of 56 tablets lasts 28 days. The cost of one 28-day cycle is therefore 123384.33 ₺.
How Alpelisib Works
- Piqray, containing alpelisib, is a kinase inhibitor effective against HR-positive, HER2-negative, PIK3CA-mutated breast cancer.
- It is a phosphatidylinositol-3-kinase (PI3K) inhibitor with specific activity against the p110α isoform.
- It blocks several key signaling pathways, including AKT.
- In HR-positive, PIK3CA-mutated breast cancer, alpelisib plus fulvestrant enhances antitumor activity compared with fulvestrant alone.
What Is a PIK3CA Mutation? How Is It Tested?
PIK3CA encodes the enzyme phosphatidylinositol-3-kinase-α (PI3Kα). The PI3Kα enzyme controls many biological functions, including cell growth, proliferation and intracellular signaling. A PIK3CA mutation can make the enzyme overactive, causing abnormal cell growth and proliferation and cancer formation. Around 40% of patients with hormone receptor (HR)-positive breast cancer have PIK3CA mutations.
PIK3CA testing generally involves genetic analysis of cancerous tissue. Techniques such as polymerase chain reaction (PCR) or next-generation sequencing (NGS) examine PIK3CA gene DNA in cell samples.
FDA Approval Timeline
- 5 April 2022: Alpelisib Received FDA Approval for PIK3CA Mutation-Related Overgrowth Spectrum.
- 24 May 2019: The FDA Approved Piqray (Alpelisib) as the First PI3K Inhibitor for Breast Cancer.
Resistance Mechanisms
- Activation of alternative pathways, including MAPK, ER, HER2, AXL, PIM-1 and FOXO transcription factors.
- Signaling through other PI3K isoforms.
- Activation of downstream PI3K pathway effectors such as AKT and mTOR.
- Loss of PTEN expression.
- Epigenomic cross-talk between PI3K and ER pathways.
Pharmacokinetics
Absorption: Oral bioavailability is approximately 25%. Peak plasma levels occur 2-4 hours after administration. Distribution: Plasma protein binding is 89%. Steady-state levels are reached in 3 days. Metabolism and Excretion: It is metabolized in the liver by CYP3A4, but elimination is primarily hepatic (81%), through the feces. The half-life is 8-9 hours.
Dosage and Drug Interactions
- Recommended Dose: 300 mg once daily (2 tablets of 150 mg).
- CYP3A4 Interactions: Enzyme inducers such as St. John’s wort and rifampin may reduce efficacy; inhibitors such as ketoconazole may increase side effects.
- Warfarin: It may alter INR values, requiring close monitoring for bleeding risk.
Important Considerations
- No dose reduction is required in mild to severe hepatic impairment.
- Monitor for severe hypersensitivity and serious skin reactions, such as Stevens-Johnson syndrome.
- Blood Glucose Monitoring: Monitor blood glucose at least weekly for the first 8 weeks.
- Patients should be prescribed antidiarrheal medication and increase oral fluid intake.
- It may harm the fetus during pregnancy; breastfeeding should be avoided.
Side Effects
- Hyperglycemia: The most common side effect (64%). It can be controlled with metformin.
- Skin Reactions: Maculopapular rash and serious conditions such as Stevens-Johnson syndrome.
- Respiratory: Pneumonitis (noninfectious lung inflammation) and shortness of breath.
- Gastrointestinal: Diarrhea, nausea, vomiting and mouth sores (mucositis).
- General: Fatigue, asthenia and anorexia.
References
- Novartis, Piqray (alpelisib) FDA Prescribing Information.
- Republic of Turkey Ministry of Health, Pimreva Authorization and Indication Form (2021).
- Alpelisib Treatment and Cost Analysis, Dr. Özdoğan Clinical Database (February 2026).
Sources
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