|Trade names||Tazverik, others|
|Drug class||EZH2 inhibitor|
|Main uses||Epithelioid sarcoma, non-Hodgkin lymphoma|
|Side effects||Pain, tiredness, nausea, decreased appetite, vomiting, constipation|
|Chemical and physical data|
|Molar mass||572.750 g·mol−1|
|3D model (JSmol)|
Tazemetostat, sold under the brand name Tazverik, is a medication used to treat epithelioid sarcoma which cannot be removed by surgery and non-Hodgkin lymphoma that has failed other treatments. It is taken by mouth.
Common side effects include pain, tiredness, nausea, decreased appetite, vomiting, and constipation. Other side effects may include secondary cancers including T-cell lymphoblastic lymphoma, myelodysplastic syndrome, and acute myeloid leukemia. It works by blocking the activity of EZH2 .
Tazemetostat was approved for medical use in the United States in 2020. As of 2021 has not been fully approved in Europe; though has been granted an orphan designation. In the United States it costs about 17,300 USD per month as of 2021.
Most cases of epithelioid sarcoma begin in the soft tissue under the skin of an extremity, though it can start in other areas of the body. Surgical removal is considered the main treatment when the cancer is localized to one area of the body. Chemotherapy or radiation may also be given. However, there is a high likelihood for local and regional spread of the disease even with treatment and approximately 50% of patients have metastatic disease at the time of diagnosis. Metastatic disease is considered life-threatening to the patient.
It is taken at a dose of 800 mg twice per day.
Mechanism of action
Tazemetostat blocks activity of the EZH2 methyltransferase, which may help keep the cancer cells from growing. According to the NCI Drug Dictionary, "tazemetostat is an orally available, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2, with potential antineoplastic activity. Upon oral administration, tazemetostat selectively inhibits the activity of both wild-type and mutated forms of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2 mutated cancer cells. EZH2, which belongs to the class of histone methyltransferases (HMTs), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation."
The U.S. Food and Drug Administration (FDA) approved tazemetostat in January 2020, based on the results of a clinical trial (NCT02601950) enrolling 62 subjects with metastatic or locally advanced epithelioid sarcoma. During the clinical trial, subjects received 800 milligrams (mg) of tazemetostat twice a day until the disease progressed or the subject reached an unacceptable level of toxicity. Tumor response assessments were performed every eight weeks during the clinical trial. The trial measured how many subjects experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate). The overall response rate was 15%, with 1.6% of subjects having a complete response and 13% having a partial response. Of the nine subjects that had a response, six (67%) subjects had a response lasting six months or longer.
The trial was conducted at 22 sites in France, United Kingdom, Taiwan, Italy, Canada, Belgium, and the United States.
The FDA granted the application for tazemetostat accelerated approval and orphan drug designation. The FDA granted the approval to Epizyme Inc. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.
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