FDA Authorizes Phase 2 Testing of Tazemetostat for Mesothelioma

The U.S. Food and Drug Administration (FDA) in early May accepted an Investigational New Drug (IND) application for a mesothelioma treatment aimed at patients with a particular defect of the BAP1 gene.

The FDA’s IND approval was granted for the drug tazemetostat. The manufacturer, Epizyme, Inc., is based in Cambridge, Massachusetts.

Getting IND approval paves the way for a Phase 2 study of tazemetostat. Epizyme said it intends to conduct this Phase 2 study during the third quarter of this year.

Epizyme is already testing tazemetostat for patients with non-Hodgkin lymphoma and certain genetically defined solid tumors, according to company CEO Robert Bazemore.  Among those tumors are ones characterized as INI1-negative and SMARCA4-negative tumors.

Epizyme wants now to see how well tazemetostat can work for mesothelioma patients. The company believes tazemetostat might prove to be a promising option for patients with BAP1 loss of function.

EZH2 Abnormality in Mesothelioma Patients

Epizyme describes tazemetostat as a small molecule inhibitor of EZH2. EZH2 is an enzyme that plays an important role in good health.

However, EZH2 activity in patients with mesothelioma and other cancers is abnormal. This abnormality takes the form of improper regulation of the genes responsible for controlling cell proliferation.

Because of improper regulation, those cell-controllers are rendered incapable of doing their intended job. This lets cancerous cells multiply.

Epizyme reports that there is a growing body of scientific evidence suggesting mesothelioma characterized by BAP1 loss of function may be slowed or perhaps even halted if this EZH2 abnormality is decreased.

Epizyme indicates that an article published in the journal Nature makes it clear why the company is targeting BAP1 loss-of-function mesothelioma. “Loss of BAP1 function leads to EZH2-dependent transformation” was written by researchers from Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College and Northwestern University.

BAP1 Function Loss Is Common in Mesothelioma

The researchers said they were able to demonstrate that BAP1 loss in mice results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) expression and boosted repression of polycomb repressive complex 2 (PRC2) targets.

They concluded that mesothelioma cells without BAP1 are sensitive to EZH2 pharmacologic inhibition. This, they said, points to the possibility of “a novel therapeutic approach for BAP1-mutant malignancies.”

As many as 60 percent of the mesothelioma cases reported each year are through to be characterized by BAP1 loss of function.

Epizyme brands itself as a clinical stage biopharmaceutical company. The firm indicates that its core business involves development of novel epigenetic cancer therapeutics for cancer patients.