FDA approval date:
metastatic or locally advanced epithelioid sarcoma
Mechanism of Action:
Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations
including Y646X and A687V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration
(IC50) of 392 nM, approximately 36 times higher than the IC50 for inhibition of EZH2.
The most well-characterized function of EZH2 is as the catalytic subunit of the polycomb repressive complex 2
(PRC2), catalyzing mono-, di-, and trimethylation of lysine 27 of histone H3. Trimethylation of histone H3
leads to transcriptional repression. SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes can antagonize
PRC2 function in the regulation of the expression of certain genes. Preclinical in vitro and in vivo models with
the loss or dysfunction of certain SWI/SNF complex members (e.g., integrase interactor 1
[INI1/SNF5/SMARCB1/BAF47], SMARCA4 and SMARCA2) can lead to aberrant EZH2 activity or
expression and a resulting oncogenic dependence on EZH2.
Tablets: 200 mg film-coated, red, round, biconvex shape and debossed with “EZM 200” on one side and plain
on the other.
The most common (≥20%) adverse reactions are pain, fatigue, nausea,
decreased appetite, vomiting, and constipation.