FDA grants Breakthrough Therapy designation to Syndax's entinostat for ER+ breast cancer

Syndax Pharmaceuticals Inc. today announced that the U.S. Food and Drug Administration (FDA) has designated entinostat as a Breakthrough Therapy for the treatment of locally recurrent or metastatic estrogen receptor-positive (ER+) breast cancer when added to exemestane in postmenopausal women whose disease has progressed following non-steroidal aromatase inhibitor therapy. Entinostat is an investigational histone deacetylase inhibitor (HDACi) set to begin Phase 3 testing in combination with exemestane in postmenopausal women with metastatic ER+ breast cancer who have progressed on hormonal therapy.

The Breakthrough Therapy designation for entinostat is based on data from the completed Phase 2 ENCORE 301 study, in which entinostat was shown to extend both progression-free survival and overall survival when added to exemestane in postmenopausal women with ER+ metastatic breast cancer whose cancer had progressed after treatment with a nonsteroidal aromatase inhibitor and with a very acceptable tolerability profile. A Phase 3 trial, planned to begin enrolling patients in the first quarter of 2014 is currently being developed by the ECOG-ACRIN Cancer Research Group, which would conduct the study under the sponsorship of the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI).

"The FDA's decision to designate entinostat a Breakthrough Therapy is important validation of the drug's therapeutic potential in women with advanced breast cancer," said Arlene M. Morris, Syndax's chief executive officer. "Currently, women with ER+ breast cancer who have progressed on hormonal therapy have limited therapeutic options. Entinostat's epigenetic mechanism may reverse resistance to hormonal therapy, delaying the need for toxic chemotherapeutic agents and improving survival when given in combination with aromatase inhibitors. This breakthrough designation will allow us to more rapidly bring this new treatment option to patients who may benefit from its availability."

The Food and Drug Administration Safety and Innovation Act (FDASIA), signed in July, 2012, created the Breakthrough Therapy Designation. According to the FDA, the designation allows the expedited development and review of a drug to treat a serious or life threatening disease or condition intended alone or in combination with one or more other drugs for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.