Entinostat

Analyst Outlook

Entinostat (Syndax Pharmaceuticals/Kyowa Hakko Kirin) may have an advantage over other pipeline

therapies in development for metastatic hormone receptor-positive (HR+)/human epidermal growth

factor receptor 2-negative (HER2-) breast cancer, because Phase II data have demonstrated that it

significantly improves overall survival (OS). If approved, entinostat will compete for relapsed

HR+/HER2- breast cancer patients with currently marketed therapies Faslodex (fulvestrant;

AstraZeneca) and Halaven (eribulin mesylate; Eisai), which have also demonstrated OS benefits in

Phase III trials.

Drug Overview

Entinostat is a class I selective histone deacetylase (HDAC) inhibitor. HDACs influence the expression

of genes involved in both the initiation of cancer and its progression through several pathways.

Specifically, class I HDACs play a role in cell survival and proliferation. Overexpression of class I HDACs

can lead to the repression of p53 and von Hippel–Lindau tumor suppressors, in addition to reductions

in the expression of the cyclin-dependent kinase (CDK) inhibitor p21. Histone deacetylation has also

been shown to cause resistance to endocrine therapies via the repression of the estrogen receptor (ER)

(Glozak and Seto, 2007; Ropero and Esteller, 2007; Sabnis et al., 2011).