Tazemetostat (Tazverik)

Mechanism of action

From the NCI Drug Dictionary: 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, E7438 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.

Diseases for which it is used

• Epithelioid sarcoma
• Follicular lymphoma

Patient drug information

• Tazemetostat (Tazverik) package insert
• Tazemetostat (Tazverik) patient drug information (Chemocare)
• Tazemetostat (Tazverik) patient drug information (UpToDate)

History of changes in FDA indication

Epithelioid sarcoma

• 2020-01-23: Granted accelerated approval for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. (Based on EZH-202)

Follicular lymphoma

• 2020-06-17: Granted accelerated approval for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies. (Based on E7438-G000-101)
• 2020-06-17: Granted accelerated approval for adult patients with R/R FL who have no satisfactory alternative treatment options. (Based on E7438-G000-101)

History of changes in PMDA indication

• 2021-06-23: Newly indicated for the treatment of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (for use only if refractory or intolerant to standard therapies).

Also known as

• Code names: E-7438, EPZ-6438
• Brand name: Tazverik