What Is Tisotumab Vedotin-tftv (Tivdak)? FDA Approval, Licensing and Reimbursement in Türkiye
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A Next-Generation Cervical Cancer Treatment: Tisotumab Vedotin (Tivdak)
- FDA Approval: Yes (first approval date: April 29, 2024)
- Brand Name: Tivdak
- Active Ingredient: Tisotumab vedotin-tftv
- Route of Administration: Intravenous infusion
- Class: Antibody–drug conjugate (ADC)
- Category: Antineoplastic (used in cancer treatment)
- Manufacturers: Seagen Inc. and Genmab A/S; marketing and distribution rights belong to Pfizer Inc.
- Approved Cancers: Tivdak is used in adults with metastatic cervical cancer that has progressed or recurred after chemotherapy.
💰 Cost and Status in Türkiye (February 2026):
- Vial price (40 mg): Approximately 7237 USD - 7445 USD per vial.
- Cost per Cycle (for a 70 kg Patient): At the standard 2 mg/kg dose (140 mg / 4 vials), the estimated drug cost per cycle is approximately 31000 USD - 34000 USD .
- Status in Türkiye: Tivdak is not yet licensed in Türkiye. It may be imported through Ministry of Health special authorization procedures for overseas medicine procurement.
- Reimbursement: Not reimbursed by SGK.
What Is Tisotumab Vedotin and How Does It Work?
Tisotumab vedotin is a biological drug in the antibody–drug conjugate (ADC) class that provides targeted treatment against selected cancer cells. It combines a monoclonal antibody that specifically interacts with tissue factor (TF), a surface protein overexpressed in some cancers, with the cytotoxic agent monomethyl auristatin E (MMAE) through a covalent bond. The structure is intended to deliver selective toxicity to cancer cells while minimizing harm to healthy cells.
Mechanism of Action
- Target Recognition and Binding: The antibody component specifically binds to tissue factor (TF), which is highly expressed on cancer-cell surfaces.
- Internalization: The drug–cell complex is then taken into the cell by endocytosis.
- Drug Release: Inside the cell, lysosomal enzymes break down the conjugate and release its cytotoxic payload, MMAE.
- Microtubule Disruption: MMAE inhibits polymerization of microtubules, a key part of the cell skeleton, stopping cell division and causing mitotic arrest.
- Apoptosis (Programmed Cell Death): Cell-cycle arrest and impaired microtubule function ultimately lead the target cancer cell into apoptosis.
FDA (US Food and Drug Administration) Approval History
- June 16, 2017: Genmab announced initial cervical cancer findings from preliminary data in a phase 1/2 tisotumab vedotin study.
- June 29, 2020: Genmab announced highly positive preliminary findings from a phase 2 trial in recurrent or metastatic cervical cancer.
- February 10, 2021: Genmab and Seagen announced submission of the tisotumab vedotin biologics license application (BLA) to the FDA.
- September 20, 2021: The FDA granted Tivdak (tisotumab vedotin-tftv) accelerated approval for previously treated recurrent or metastatic cervical cancer.
- April 29, 2024: The FDA granted Tivdak full approval for recurrent or metastatic cervical cancer.
Mechanisms of Resistance
- Reduced Target Antigen (TF) Expression: Reduced TF expression decreases drug binding and internalization.
- Impaired Endocytosis and Intracellular Transport: If cellular uptake is disrupted, the active toxin MMAE cannot be released.
- Resistance to MMAE: Some cancer cells may develop resistance by changing microtubule protein isoforms.
- Drug Efflux Pumps: Cell-membrane transporters such as P-gp/MDR1 may expel the active toxin MMAE from the cell.
Pharmacokinetics
Absorption: Intravenous administration provides 100% bioavailability. Distribution: Total volume of distribution (Vd) is approximately 2.4 L. Metabolism: MMAE is metabolized in the liver by CYP3A4 . Elimination: Mean elimination half-life (t1/2) is approximately 4 days.
Dose Range
- Calculated as 2 mg/kg body weight (maximum 200 mg).
- Repeated every 3 weeks (every 21 days).
- Dose reductions: first to 1.3 mg/kg, then to 1.0 mg/kg.
Points Requiring Attention
- Severe ocular toxicities may occur. Eye toxicity, including conjunctivitis, dry eye, corneal lesions, and blurred vision, is among the most frequent and clinically important adverse reactions. Eye examinations before and during treatment, preventive eye drops, cold compresses, and ophthalmology consultation when necessary are recommended.
- Peripheral neuropathy may occur, particularly numbness, tingling, or burning in the hands and feet. Worsening symptoms may require dose reduction or discontinuation.
- Bleeding may occur. Tissue factor (TF), the drug's target, also participates in blood clotting. Patients should be carefully monitored particularly for nosebleeds, gum bleeding, or bleeding between menstrual periods.
- There is a risk of serious infection because neutropenia (decreased white blood cells) may develop. Patients should be alerted to fever, sore throat, and urinary infection symptoms, with precautions when infection risk is high.
- Diarrhea and gastrointestinal adverse reactions are common and may disrupt fluid and electrolyte balance. Moderate to severe diarrhea requires supportive care and, if necessary, longer intervals between doses.
- It is contraindicated in pregnancy because fetal harm is considered possible. Women of reproductive age should use effective contraception and avoid pregnancy during treatment and for at least 4 months after the final dose.
- Reproductive toxicity may also occur in male patients. They should take precautions to prevent pregnancy in their partners during treatment and for at least 4 months after the final dose.
Adverse Reactions
- Dry eye 40%
- Conjunctivitis 26%
- Peripheral neuropathy 42%
- Fatigue 39%
- Nausea 33%
- Diarrhea 26%
- Anemia 25%
- Nosebleeds 25%
- Hair loss 27%
References
- TIVDAK (tisotumab vedotin-tftv) FDA Prescribing Information.
- Genmab and Seagen Clinical Announcements (2017-2024).
- U.S. Drug Pricing and Cost Analysis Reports (2025-2026).
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