Vintafolide is an investigational targeted cancer therapeutic currently under development by

Endocyte Endocyte ( NASDAQ: ECYT) is a biopharmaceutical company established in 1996 and headquartered in West Lafayette, Indiana, a resident of the Purdue Research Park. In 2011 the company completed successfully an initial public offering (IPO). , the ...

and Merck & Co. It is a small molecule drug conjugate consisting of a

small molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ...

targeting the folate receptor, which is overexpressed on certain cancers, such as

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different c ...

, and a potent chemotherapy drug,

vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...

. Vintafolide is designed to deliver the toxic vinblastine drug selectively to cells expressing the folate receptor using folate targeting. It is being developed with a companion imaging agent, etarfolatide, that identifies patients that express the folate receptor and thus would likely respond to the treatment with vintafolide. A Phase 3 study evaluating vintafolide for the treatment of

platinum-resistant ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cel ...

(PROCEED trial) and a Phase 2b study(TARGET trial) in

non-small-cell lung carcinoma Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

(NSCLC) are ongoing (in 2012). A Marketing Authorization Application (MAA) filing for vintafolide and etarfolatide for the treatment of patients with folate receptor-positive platinum-resistant

in combination with

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

, pegylated liposomal doxorubicin (PLD), has been accepted by the European Medicines Agency. The drug received

orphan drug status An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment o ...

in Europe in March 2012. Merck & Co. acquired the development and marketing rights to this experimental cancer drug from

in April 2012.

remains responsible for the development and commercialization of etarfolatide, a non-invasive companion imaging agent used to identify patients expressing the folate receptor that will likely respond to treatment with vintafolide. In 2014 Merck and Endocyte stopped a late-stage study (PROCEED) of vintafolide in treating ovarian cancer on the recommendation of a data safety monitoring board, saying that the drug failed to improve progression-free survival.

Mechanism of action

Folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...

is required for cell division, and rapidly dividing

cancer cell Cancer cells are cells that divide continually, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these d ...

s often express folate receptors in order to capture enough

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...

to support rapid cell growth. Elevated expression of the folate receptor occurs in many diseases, including other aggressively growing

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

s and

inflammatory disorders Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

. Vintafolide binds to the folate receptor and is subsequently taken up by the cell through a natural internalization process called endocytosis. Once inside the cell, vintafolide’s linker releases the

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

drug which kills the cell.

References

{{Intracellular chemotherapeutic agents Experimental cancer drugs Folates