Tisotumab vedotin, sold under the brand name Tivdak, is an

antibody-drug conjugate Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 phar ...

used to treat cervical cancer. It is a combination of tisotumab, a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

against tissue factor, and

monomethyl auristatin E Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody (MAB) which directs it to the cancer cells. In International Nonpropr ...

(MMAE), a potent inhibitor of cell division. It is administered by

infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An in ...

into a vein. Tisotumab vedotin was approved for medical use in the United States in September 2021. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

considers it to be a first-in-class medication.

Adverse effects

In the United States, Tivdak carries a

black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it ...

for ocular toxicity, which occurs in up to 60% of treated patients. In clinical trials, the most common forms of ocular toxicity were

dry eye Dry or dryness most often refers to: * Lack of rainfall, which may refer to **Arid regions **Drought * Dry or dry area, relating to legal prohibition of selling, serving, or imbibing alcoholic beverages * Dry humor, deadpan * Dryness (medical) * ...

conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

l damage, and blepharitis. Other common adverse effects include bleeding (occurring in approximately 60% of patients, most often

nosebleed A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bl ...

) and

peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...

(42% of patients). Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs.

Mechanism of action

The antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor, a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by

proteolytic cleavage Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

, releasing MMAE, which stops the cell cycle and kills the cell by apoptosis.

History

Tisotumab vedotin was developed by

Genmab Genmab A/S is a Danish biotechnology company, founded in February 1999 by Florian Schönharting, at the time managing director of BankInvest Biomedical venture fund. The company is based in Copenhagen, Denmark - internationally, it operates thr ...

in Utrecht, the Netherlands, and

Copenhagen, Denmark Copenhagen ( or .; da, København ) is the capital and most populous city of Denmark, with a proper population of around 815.000 in the last quarter of 2022; and some 1.370,000 in the urban area; and the wider Copenhagen metropolitan ar ...

, with the code name TF-011-MMAE. In September 2021, tisotumab vedotin was granted accelerated approval by United States

for the use of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Society and culture

Names

Tisotumab vedotin is the international nonproprietary name. Tivdak is the brand name for tisotumab vedotin in the United States.

References

External links

* * * * * Antibody-drug conjugates Monoclonal antibodies for tumors {{pharma-stub