What Is Telisotuzumab Vedotin (Emrelis)? FDA Approval, Licensing in Turkey, and Reimbursement

• FDA Approval: Yes (Initial approval date: May 14, 2025)
• Brand Name: Emrelis
• Active Ingredient: Telisotuzumab vedotin-tllv
• Route of Administration: Intravenous (IV) infusion (administered into a vein)
• Class: Antibody-drug conjugate (ADC)
• Category: Targeted biological treatment
• Manufacturer: AbbVie Inc.
• Availability in Turkey: Not yet licensed in Turkey.
• Approved Cancer Indications: Approved for adults with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC), high c-Met protein overexpression, and previous systemic treatment.

What Is Telisotuzumab Vedotin (Emrelis)? How Does It Work?

Telisotuzumab vedotin, marketed as Emrelis, is a targeted antibody-drug conjugate (ADC) used to treat advanced non-small cell lung cancer (NSCLC). It is designed specifically to target tumor cells expressing high levels of c-Met protein. In 2025, it received accelerated approval from the US Food and Drug Administration (FDA) for previously systemically treated patients with NSCLC and high c-Met expression.

How Does It Work?

• Target recognition: The antibody component binds specifically to a surface protein called c-Met (hepatocyte growth factor receptor), which is overexpressed in some cancers. This receptor is associated with cell growth, survival, and metastasis.
• Cellular uptake (internalization): After the antibody binds to the c-Met receptor, the tumor cell takes up the complex.
• Release of the toxic agent: Inside the cell, the cytotoxic agent linked to the antibody, monomethyl auristatin E (MMAE), is released. MMAE targets microtubules, preventing cell division and initiating apoptosis (programmed cell death).
• Selective cytotoxicity: Through this mechanism, only tumor cells with high c-Met expression are targeted, while healthy cells are spared as much as possible.

Clinical Significance

Telisotuzumab vedotin offers a new treatment option for patients with NSCLC who have not responded to systemic treatment, particularly those without EGFR or ALK mutations. Its target-specific mechanism provides a more selective and potentially more tolerable profile than chemotherapy.

FDA (US Food and Drug Administration) Approval History

• May 14, 2025: The FDA granted accelerated approval to Emrelis (telisotuzumab vedotin-tllv) for previously treated patients with non-small cell lung cancer (NSCLC) showing high c-Met protein overexpression.
• September 27, 2024: AbbVie submitted a Biologics License Application to the US Food and Drug Administration (FDA) for telisotuzumab vedotin (Teliso-V) for previously treated patients with non-small cell lung cancer.
• November 29, 2023: AbbVie announced positive preliminary results from the phase 2 LUMINOSITY trial evaluating telisotuzumab vedotin (Teliso-V) in previously treated patients with non-small cell lung cancer (NSCLC).
• January 4, 2022: AbbVie announced that the FDA had granted Breakthrough Therapy designation to telisotuzumab vedotin (Teliso-V) for previously treated patients with non-small cell lung cancer.

Licensing in Turkey

It is not currently officially licensed in Turkey. It is not included in the current "Active Overseas Medicines List" published by the Turkish Pharmacists' Association (TEB).

Mechanisms of Resistance

• Reduced or Lost c-Met Expression: If expression of the drug's target, the c-Met receptor, decreases on the tumor cell surface, the drug cannot bind adequately or enter the cell. This may allow the cell to evade the drug.
• Impaired Internalization (Cellular Uptake): After binding, ADCs are taken into the cell, where they release their toxic payloads, such as MMAE. If this uptake process involving the c-Met receptor becomes ineffective, the drug cannot exert its effect inside the cell.
• Impaired Lysosomal Processing: After entering the cell, telisotuzumab vedotin is broken down in lysosomes, releasing the toxic agent MMAE. Impaired lysosomal activity may reduce the effectiveness of this toxic agent.
• Increased Multidrug Resistance (MDR) Proteins: Tumor cells may overproduce drug transport pumps such as P-gp (P-glycoprotein), which pump chemotherapeutic agents such as MMAE out of the cell. This reduces the drug's cytotoxic effect.
•  Specific Resistance to Microtubule-Targeting Drugs: The MMAE carried by telisotuzumab vedotin targets microtubules. Cells may develop resistance to this toxic agent through changes or mutations in β-tubulin isoforms.
• Activation of Alternative Signaling Pathways: Tumor cells may continue to grow by activating pathways that bypass c-Met signaling, such as EGFR, PI3K/AKT, and KRAS. This may reduce the effectiveness of the targeted treatment.

Absorption

Because telisotuzumab vedotin is administered by intravenous (IV) infusion, gastrointestinal absorption does not occur. Its bioavailability is therefore close to 100%, with direct entry into the systemic circulation. The absorption phase is characterized by a rapid rise in plasma concentration after administration.

Distribution

In the circulation, the drug is predominantly present in its monoclonal antibody-conjugated form. Antibody-drug conjugates generally have limited extravascular distribution because their large molecular structures cannot freely cross cell membranes. Telisotuzumab vedotin achieves target-specific distribution by moving toward tumor tissues with high c-Met receptor expression. Its volume of distribution (Vd) is limited, mainly to plasma and interstitial fluid.

Metabolism

The biological activity of telisotuzumab vedotin results from the combination of two separate components:

• The antibody component binds to c-Met on the cell surface, enabling entry into the cell.
• After internalization, it undergoes proteolytic breakdown by lysosomal enzymes.

The cytotoxic agent monomethyl auristatin E (MMAE) released in this process enters the cytoplasm, disrupts microtubule dynamics, and inhibits cell division. MMAE is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme. This creates the potential for interactions with CYP3A4 inducers or inhibitors. 

Elimination

The conjugated antibody component is cleared primarily through the reticuloendothelial system (RES). After metabolism, MMAE is excreted mainly through bile into feces and, to a lesser extent, in urine. The reported average elimination half-life of telisotuzumab vedotin is approximately 2-4 days, although it may be shorter for the MMAE component.

Dosing Schedule

• Dose: 1.9 mg/kg
• Maximum Dose: 190 mg (for patients weighing ≥100 kg)
• Route of Administration: Intravenous infusion
• Dosing Frequency: Every 2 weeks (every 14 days)
• Treatment Duration: Continue until disease progression or the development of intolerable toxicity.
• First dose reduction: 1.6 mg/kg
• Second dose reduction: 1.3 mg/kg
• Third dose reduction: 1.0 mg/kg
• If intolerable toxicity occurs: Treatment must be permanently discontinued.

Drug Interactions

Interactions With the CYP3A4 Enzyme System: MMAE is metabolized mainly by the hepatic enzyme CYP3A4. Medicines that affect CYP3A4 may therefore increase or decrease plasma MMAE levels.

• CYP3A4 inhibitors (medicines that reduce enzyme activity): Ketoconazole, itraconazole, clarithromycin, ritonavir, and verapamil. These medicines may increase MMAE levels and the risk of toxicity, particularly neutropenia and peripheral neuropathy. Concomitant use should be avoided if possible, or the patient should be monitored closely.
• CYP3A4 inducers (medicines that increase enzyme activity): Rifampin, carbamazepine, phenytoin, and St. John's wort (Hypericum). These medicines may accelerate MMAE metabolism, reducing its plasma level and potentially its effectiveness. Concomitant use is not recommended.

P-Glycoprotein (P-gp) Interactions: MMAE is also a P-gp substrate. P-gp inhibitors, such as verapamil and amiodarone, may reduce the removal of MMAE from cells, creating a risk of increased toxicity.

Medicines Used During Infusion: Because telisotuzumab vedotin is given by intravenous infusion, caution is needed regarding potential physical or chemical incompatibility with other IV medicines administered during the infusion. It should not be mixed with other cytotoxic agents in the same infusion line.

Precautions

• Interstitial Lung Disease / Pneumonitis: Pulmonary toxicity has been reported with ADCs, particularly those containing MMAE. If patients develop symptoms such as dyspnea, cough, fever, or hypoxia, treatment should be stopped and an assessment performed. Corticosteroid treatment should be considered if necessary. Patients should be monitored closely for respiratory symptoms before and during treatment.
• Myelosuppression (Neutropenia, Anemia, Thrombocytopenia): Telisotuzumab vedotin may suppress bone marrow function. Neutropenia, in particular, is a dose-limiting toxicity. A complete blood count should be performed before each cycle, and the dose should be reduced or delayed if necessary.
• Peripheral Neuropathy: MMAE may cause sensory neuropathy through microtubule inhibition. Symptoms may include numbness, tingling, and loss of sensation. A neurological examination should be performed, and dose reduction or treatment interruption should be considered in severe cases.
• Hepatic Impairment: MMAE is metabolized in the liver by CYP3A4. It should be used cautiously in patients with mild-to-moderate hepatic impairment. It is not recommended in severe hepatic impairment because data are insufficient. Liver function tests (AST, ALT, bilirubin) should be monitored regularly before and during treatment.
•  Older and Frail Patients: Older patients may have an increased risk of toxicity, particularly myelosuppression and neuropathy. Careful dose titration is recommended in patients with poor performance status.
• Pregnancy and Breastfeeding: Animal studies have shown that MMAE causes embryo-fetal toxicity. Use is also not recommended during breastfeeding because of the potential for harm. Women of childbearing potential should undergo a pregnancy test before treatment. Effective contraception is recommended during treatment and for at least 6 months afterward. Breastfeeding should be stopped during treatment and for at least 1 week afterward.
• Increased Risk From Drug Interactions: Concomitant CYP3A4 inhibitors or inducers may alter MMAE levels, increasing toxicity or creating a risk to treatment effectiveness. If concomitant use is necessary, the patient should be monitored closely.

Adverse Effects

• Peripheral neuropathy 38%
• Fatigue 33%
• Shortness of breath (dyspnea) 30%
• Loss of appetite 25%
• Nausea – 23%
• Cough 23%
• Rash 21%
• Diarrhea 20%
• Thrombocytopenia (low platelet count) 18%
• Anemia 18%
• Neutropenia 16%
• Constipation 16%
• Weakness 15%
• Elevated liver enzymes (AST/ALT) 14%
• Dizziness 11%
• Weight loss 10%