What Is Axitinib (Inlyta)? FDA Approval, Licensing and Reimbursement in Turkey

• FDA Approved: Yes (Initial approval date: January 27, 2012)
• Brand Name: Inlyta
• Active Ingredient: Axitinib
• Route of Administration: Oral, tablet form
• Class: Signal transduction inhibitor, antiangiogenic agent
• Category: Targeted agent
• Manufacturer: Pfizer
• Distribution in Turkey: Pfizer
• Approved Cancers: Advanced kidney cancer (renal cell carcinoma, RCC)

What Is Inlyta, Containing Axitinib?

Inlyta, containing axitinib, is a small-molecule drug that inhibits VEGFR-1, VEGFR-2 and VEGFR-3 tyrosine kinases, preventing tumors from forming blood vessels. This reduces tumor growth and metastasis.

How Does It Work?

• As a small-molecule inhibitor, axitinib inhibits the ATP-binding sites of VEGFR-1, VEGFR-2 and VEGFR-3 tyrosine kinases.
• It has limited effects on platelet-derived growth factor (PDGFR) and c-Kit (CD117).
• It interferes with tumor growth, proliferation, metastasis and angiogenesis.

FDA (US Food and Drug Administration) Approval History

• May 14, 2019 – The FDA approved Bavencio (avelumab) with Inlyta (axitinib) for patients with advanced renal cell carcinoma (RCC).
• April 22, 2019 – The FDA approved Keytruda (pembrolizumab) with Inlyta (axitinib) as first-line treatment for patients with advanced renal cell carcinoma (RCC).
• January 27, 2012 – The FDA approved Inlyta (axitinib) for advanced renal cell carcinoma (RCC).

Licensing in Turkey

Inlyta (axitinib) is licensed in Turkey for the following therapeutic indications:

Therapeutic Indications:

1. For the Treatment of Advanced Renal Cell Carcinoma: previously treated patients with advanced renal cell carcinoma (RCC) in whom at least one systemic treatment has failed are eligible for monotherapy.

2. Axitinib with pembrolizumab is indicated as first-line treatment of adults with metastatic clear-cell renal carcinoma, a Karnofsky performance score ≥ 70, no symptomatic brain metastases, no uncontrolled hypertension and intermediate/poor IMDC risk.
3. Axitinib with axitinib is indicated as first-line treatment of adults with advanced PD-L1-positive clear-cell renal cancer.

Treatment duration: Combination treatment is given until disease progression or intolerable side effects.

The following diagnoses qualify for off-label use without additional TİTCK approval:

1. Advanced hemangiopericytoma: Appropriate for use after one line of systemic chemotherapy.
2. Metastatic adenoid cystic carcinoma: Appropriate for use after progression following chemotherapy for metastatic disease.

Is Inlyta Reimbursed in Turkey?

Inlyta's treatment settings covered by Turkey's Social Security Institution (SGK) are as follows:

Treatment of Advanced Renal Cell Carcinoma:

SGK covers monotherapy for patients with advanced renal cell carcinoma (RCC) after one prior systemic treatment has failed. Patients must have an ECOG performance status of 0-1 before starting treatment.

Treatment Duration: Treatment continues until disease progression or intolerable toxicity.

First-Line Combination Treatment:

1. Axitinib with pembrolizumab is indicated as first-line treatment of adults with metastatic clear-cell renal carcinoma, a Karnofsky performance score ≥ 70, no symptomatic brain metastases, no uncontrolled hypertension and intermediate/poor IMDC risk.
2. Axitinib with axitinib is indicated as first-line treatment of adults with advanced PD-L1-positive clear-cell renal cancer.

Treatment duration: Combination treatment is given until disease progression or intolerable side effects.

 The following diagnoses qualify for off-label use without additional TİTCK approval:

1. Advanced hemangiopericytoma: Appropriate for use after one line of systemic chemotherapy.
2. Metastatic adenoid cystic carcinoma: Appropriate for use after progression following chemotherapy for metastatic disease.

Price: As of August 2025, Inlyta prices are: 1mg, 56 tablets, 12774.36 TL; 3 mg, 56 tablets, 38102.81 TL; 5 mg, 56 tablets, 63430.99 TL; and 7 mg, 56 tablets, 88751.07 TL. 

Mechanisms of Resistance

• Increased expression of VEGFR-1, VEGFR-2 and VEGFR-3: Greater production of these receptors can accelerate tumor growth and spread.
• Activation of the angiogenic switch through increased expression of alternative proangiogenic pathways: The tumor activates alternative pathways to form new blood vessels.
• Increased expression of VEGF and other proangiogenic factors with greater pericyte coverage of tumor vessels: This makes tumor vessels stronger and more resilient.
• Recruitment of proangiogenic inflammatory cells from bone marrow, such as tumor-associated macrophages, monocytes and myeloid-derived suppressor cells (MDSCs): These cells help the tumor form new blood vessels and grow.

Absorption

 Axitinib (Inlyta) is rapidly absorbed when taken with food. Bioavailability is approximately 60%. Peak blood levels occur within 2-6 hours of taking it. With regular use, blood levels generally stabilize within 2-3 days.

Distribution

Axitinib (Inlyta) is 99% bound to blood proteins, meaning that most of the drug travels attached to plasma proteins. It binds particularly to albumin and alpha-1-acid glycoprotein during transport and is released where it needs to act. This helps it remain in the body longer and exert its effect.

Dose Range

The recommended starting dose for kidney cancer (renal cell carcinoma, RCC) is 5 mg PO bid, taken orally 2 times daily. 

NOTE: PO means that the drug is taken orally, while bid means that it should be taken twice daily.

The dose may be increased or reduced according to tolerability and safety. After being tolerated for at least 2 weeks, it may be increased to 7 mg PO bid and then 10 mg PO bid. To reduce the risk of adverse effects, it may be reduced to 3 mg PO bid and then 2 mg PO bid.

Metabolism

Axitinib (Inlyta) is metabolized mainly in the liver, primarily by CYP3A4 and CYP3A5 . Smaller contributions come from CYP1A2, CYP2C19 and UGT1A1 . The metabolites formed in the liver are less active than the parent drug. Elimination is mainly through feces (40%), with some excreted in urine (23%) and 12% excreted unchanged. Its half-life is 2-5 hours.

Precautions

1. Blood pressure should be controlled before treatment and monitored regularly during treatment, using antihypertensive medication if needed.
2. Patients should be informed about arterial and venous thromboembolic risks, including myocardial ischemia and stroke.
3. Axitinib should be stopped at least 24 hours before planned surgery.
4. Thyroid function tests and TSH should be monitored regularly during treatment.
5. Liver function tests and serum bilirubin should be monitored during axitinib treatment.
6. Seville oranges, star fruit, pomelo, grapefruit and grapefruit products should be avoided during treatment.
7. Pregnancy category D. It should not be used during pregnancy or breastfeeding.

Side Effects

1. High blood pressure (hypertension): Occurs in 40% of patients.
2. Arterial and venous thromboembolic events: Increased risk of blood clots.
3. Bleeding complications: Risk of serious bleeding.
4. Gastrointestinal perforations: Perforation of the stomach or intestines and wound-healing problems.
5. Diarrhea, nausea/vomiting and constipation: Common digestive problems.
6. Proteinuria: Urinary protein loss in up to 10% of patients.
7. Hypothyroidism: Reduced thyroid function.
8. Elevated liver enzymes: Increased SGOT/SGPT and serum bilirubin.
9. Reversible posterior leukoencephalopathy syndrome (RPLS): Rare serious effects (less than 1%), including headache, seizures, lethargy, confusion and blindness.