What Is Brigatinib (Alunbrig)? FDA Approval, Licensing and Reimbursement in Turkey

Brigatinib (Alunbrig)

• FDA Approved: Yes (Initial approval date: April 28, 2017)
• Brand Name: Alunbrig
• Active Ingredient: Brigatinib
• Route of Administration: Oral tablets
• Class: Signal Transduction Inhibitor, ALK Inhibitor
• Category: Targeted agent
• Manufacturer: Takeda Pharmaceuticals
• Distribution in Turkey: Takeda İlaçları San. ve Tic. A.Ş.
• Approved Cancer Indications: ALK-positive metastatic non-small cell lung cancer

What Is Alunbrig, Containing Brigatinib?

Brigatinib, the active ingredient in Alunbrig, treats ALK-positive metastatic non-small cell lung cancer. It is a small-molecule anticancer drug developed as an ALK inhibitor, used in patients with ALK mutations to slow tumor growth.

What Is an ALK Inhibitor?

ALK inhibitors target a receptor tyrosine kinase known as anaplastic lymphoma kinase (ALK). Mutations or rearrangements in ALK cause uncontrolled cancer cell growth. By blocking this receptor's activity, ALK inhibitors stop cancer cells from growing and spreading. They offer an effective option particularly for patients carrying ALK mutations.

How Does It Work?

Brigatinib is a small-molecule ALK tyrosine kinase inhibitor. It inhibits multiple receptor tyrosine kinases, including ALK, IGF-1R, ROS1, FLT-3, and EGFR mutations. This mechanism stops tumor growth, new blood vessel formation (angiogenesis), and cancer spread to other parts of the body (metastasis). It retains activity in crizotinib-resistant ALK-positive tumors.

• It is active against ALK mutations such as L1196M, G1202R, C1156Y, F1174L, and R1275Q.

📜 FDA (United States Food and Drug Administration) Approval History

• May 22, 2020: The FDA approved Alunbrig(brigatinib) for ALK+ metastatic NSCLC as a first-line treatment option.
• April 28, 2017: Takeda announced that Alunbrig(brigatinib) had received accelerated FDA approval.

🇹🇷 Licensing in Turkey

The conditions and therapeutic indications for which Alunbrig is licensed in Turkey are listed as follows:

Therapeutic Indications:

Advanced ALK-Positive NSCLC Without Prior ALK-Targeted Treatment:
Alunbrig (brigatinib) is indicated until disease progression in advanced NSCLC with confirmed ALK positivity (rearrangement/fusion detected by standardized FISH, RT-PCR, or next-generation sequencing, or positive ALK immunohistochemistry).

ALK-Positive Advanced or Metastatic NSCLC Previously Treated with Crizotinib:
Alunbrig (brigatinib) is indicated until disease progression in confirmed ALK-positive advanced or metastatic NSCLC previously treated with crizotinib.

💳 Reimbursement & Price

Alunbrig is covered by Turkey's Social Security Institution (SGK) in the following treatment situations:

1. In patients with confirmed ALK-positive advanced NSCLC, when used as first-line monotherapy, the costs are covered by SGK until disease progression.
2. In ALK-positive advanced/metastatic NSCLC previously treated with crizotinib, when used as second-line treatment, the costs are covered by SGK until disease progression.

Price (March 2026): Retail pharmacy prices for Alunbrig tablet starter packs

• 30 mg: 24145.26 TL
• 90 mg: 72551.50 TL
• 180 mg: 110172.41 TL

🧬 Mechanisms of Resistance

• Compound ALK mutations (e.g., L1196M and G1202R) may contribute to resistance to certain ALK inhibitors.
• NTRK fusions may emerge as an alternative/bypass resistance mechanism in some cases.

📦 Pharmacokinetics

Absorption: Average time to peak levels is 1–4 hours. High-fat foods reduce C_maxby 13% without significantly affecting AUC. It can be taken with or without food.

Distribution: Approximately 66% is bound to plasma proteins; steady state is reached in about 15 days.

Metabolism / Excretion: Metabolized by CYP3A4 and CYP2C8. Excretion is 65% in feces and 25% in urine; terminal half-life is approximately 25 hours.

💊 Dosing Interval

• For the first 7 days, the recommended once-daily dose is 90 mg PO.
• If tolerated, the once-daily dose can be increased to 180 mg.

🔄 Drug Interactions

• CYP3A inhibitors (ketoconazole, itraconazole, erythromycin, clarithromycin, voriconazole, etc.) → brigatinib metabolism may decrease, levels ↑, toxicity risk ↑.
• CYP3A inducers (rifampin, phenytoin, phenobarbital, carbamazepine, St. John’s Wort, etc.) → levels ↓, risk of reduced efficacy ↑.

⚠️ Precautions

1. Liver function: Careful monitoring is recommended in hepatic impairment.
2. Kidney function: Data may be limited in severe renal impairment; close monitoring is needed.
3. Anticoagulants: PT/INR monitoring is recommended for patients taking warfarin.
4. Pulmonary symptoms: New or worsening cough, shortness of breath, or similar symptoms require assessment.
5. Hyperglycemia: Blood glucose should be checked regularly in patients with diabetes or steroid use.

🤒 Adverse Effects

Adverse effects associated with brigatinib have been reported in the following order of frequency:

• Hepatotoxicity: Liver injury with elevated SGOT/SGPT may occur.
• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.
• Pulmonary toxicity: Cough, shortness of breath, fever; interstitial lung disease/pneumonia in severe cases.
• Fatigue / decreased appetite
• Cardiac: Sinus bradycardia, hypertension.
• Hyperglycemia
• Visual disturbances: Blurred vision, double vision, etc.
• Elevated CPK
• Elevated Amylase/Lipase
• Peripheral edema