What Is Yondelis (Trabectedin)? FDA Approval, Turkish Authorization, and Reimbursement

• FDA Approved: Yes (initial approval: October 23, 2015)
• Pack Name: Yondelis
• Active Ingredient: Trabectedin
• Administration: Intravenous (IV) infusion
• Class: Alkylating agent
• Category: Chemotherapy medicine
• Manufacturer: Janssen/Johnson & Johnson
• Distribution in Turkey: Onko İlaç San. ve Tic. A.Ş.
• Approved Cancers:
  • Unresectable or Metastatic Liposarcoma and Leiomyosarcoma:
    • FDA-approved for patients previously treated with anthracycline-containing regimens.

What Is Yondelis?

Yondelis, containing trabectedin, is an intravenous chemotherapy used for unresectable or metastatic liposarcoma and leiomyosarcoma. It aims to slow tumor growth and disease progression in patients previously treated with anthracycline-containing regimens.

What Is an Alkylating Agent?

Alkylating agents are anticancer medicines that bind DNA, disrupt the cell cycle, and cause cell death. They inhibit cancer-cell proliferation by impairing DNA synthesis and function. Yondelis stands out for its distinctive mechanism within this group.

How Does It Work?

Yondelis (trabectedin) exerts antitumor activity by binding DNA and affecting the tumor microenvironment:

• DNA Binding and Inhibition of DNA Repair:
  • Trabectedin binds the N2 position of guanine residues in the DNA minor groove, disrupting DNA structure and forming adducts.
  • DNA adducts cause single- and double-strand breaks and inhibit DNA synthesis and function.
• Cell-Cycle Arrest and Induction of Cell Death:
  • Arrests the cell cycle and induces apoptosis (cell death) through a p53-independent mechanism.
• Effects on the Tumor Microenvironment:
  • Inhibits production of proinflammatory and proangiogenic mediators, suppressing inflammation and new vessel formation in the tumor microenvironment.
  • Has cytotoxic effects on tumor-associated macrophages and monocytes.
• Phase-Independent Antitumor Activity:
  • Acts on cancer cells throughout all phases of the cell cycle.

FDA (United States Food and Drug Administration) Approval History

• October 23, 2015:
  • Approval: The FDA approved Yondelis (trabectedin) for certain soft-tissue sarcomas (liposarcoma and leiomyosarcoma).
• February 3, 2015:
  • Priority Review: The FDA granted Yondelis (trabectedin) priority review status for treatment of advanced soft-tissue sarcoma.
• November 24, 2014:
  • New Drug Application (NDA): Janssen submitted an NDA to the FDA for Yondelis (trabectedin) for advanced soft-tissue sarcoma.
• April 29, 2011:
  • Application Withdrawal: Centocor Ortho Biotech Products, L.P. voluntarily withdrew the New Drug Application (NDA) for trabectedin.
• September 10, 2009:
  • Complete Response Letter: The FDA issued a "Complete Response Letter" for trabectedin combined with Doxil.
• November 20, 2008:
  • Application: Ortho Biotech submitted an NDA to the FDA for trabectedin for recurrent ovarian cancer.  

Authorization in Turkey

Yondelis's licensed therapeutic indications in Turkey are stated as follows:

Therapeutic Indications

Indicated as salvage treatment after progression in locally advanced or metastatic leiomyosarcoma and liposarcoma previously treated with adequate doses and durations of doxorubicin- and ifosfamide-containing chemotherapy.

Is Yondelis Reimbursed?

The Turkish Social Security Institution (SGK) reimburses Yondelis in the following treatment settings:

SGK covers salvage use after progression in locally advanced or metastatic leiomyosarcoma and liposarcoma previously treated with adequate doses and durations of doxorubicin- and ifosfamide-containing chemotherapy.

Price: As of August 2025, the pharmacy retail price of Yondelis 1 mg 1 vial is 61526.89 ₺.

Resistance Mechanisms

• Multidrug Resistance:
  • Increased drug-efflux transporters such as P170 glycoprotein may promote removal of the drug from cells and reduce effectiveness.
• Increased ABCB1 Transporter Protein Expression:
  • Increased ABCB1 prevents accumulation of the medicine inside cells.
• Increased IGF-1R and Insulin Receptor Substrate:
  • Increases in these growth-promoting factors may cause drug resistance.
• Increased Zinc Finger Proteins (ZNF93 and ZNF43):
  • Greater activity of DNA-binding proteins that affect repair mechanisms may lead to resistance.

Pharmacokinetic Properties

• Absorption
  • Given intravenously, with no oral bioavailability.
• Distribution
  • Steady-state volume of distribution exceeds 5000 L.
  • Approximately 97% binds to plasma proteins.
• Metabolism
  • Metabolized in the liver by CYP3A4 microsomal enzymes.
  • Most is excreted in feces through the hepatobiliary system (58%). Renal elimination accounts for only 6% of total excretion.
  • Terminal half-life is approximately 175 hours.
• Dosing Interval
  • The recommended dose is 1.5 mg/m² as a 24-hour infusion every 3 weeks.
  • Administration must be through a central venous line.

Drug Interactions

• Medicines That Reduce Metabolism:
  • CYP3A4 inhibitors such as ketoconazole, itraconazole, and erythromycin may increase toxicity.
• Medicines That Accelerate Metabolism:
  • Inducers such as rifampin, phenytoin, and carbamazepine may reduce effectiveness.

Precautions

• Hepatic Dysfunction:
  • Dose reduction is recommended for moderate hepatic dysfunction. The recommended dose is 0.9 mg/m².
  • Yondelis must not be used in severe hepatic dysfunction.
• Renal Dysfunction:
  • No dose adjustment is needed in mild or moderate renal dysfunction.
• CYP3A4 Drug Interactions:
  • Concomitant use with strong CYP3A4 inhibitors (such as ketoconazole or itraconazole) or inducers (such as rifampin or phenytoin) requires careful assessment. They may alter Yondelis's effectiveness or toxicity.
• Method of Administration:
  • Yondelis must be given intravenously only, through a central venous catheter.
• Clinical Monitoring:
  • Liver function, hematological parameters, and kidney function should be monitored regularly during treatment.

Side Effects

• Myelosuppression and Neutropenia:
  • Serious and fatal neutropenic sepsis may develop due to neutropenia.
• Rhabdomyolysis and Musculoskeletal Toxicity:
  • Muscle breakdown and skeletal-system toxicities may occur.
• Hepatotoxicity:
  • ALT/AST, bilirubin, and alkaline phosphatase may increase.
• Cardiac Toxicity:
  • Reduced left ventricular ejection fraction, diastolic dysfunction, congestive heart failure (CHF), and heart failure may occur.
• Gastrointestinal Toxicity:
  • Nausea, vomiting, constipation, and diarrhea may occur.
• Fatigue and Anorexia:
  • Fatigue and loss of appetite are other common side effects.