FDA Approval Announcement
Epizyme, a biopharmaceutical company dedicated to developing novel epigenetic therapies, recently announced that the U.S. Food and Drug Administration (FDA) has approved the epigenetic drug Tazverik (tazemetostat) for two distinct indications in follicular lymphoma (FL):
Adult patients with relapsed or refractory (R/R) FL whose tumors are EZH2 mutation‑positive as detected by an FDA‑approved test, and who have received at least two prior systemic therapies.
Adult patients with R/R FL for whom no satisfactory alternative treatment options exist.
These indications were approved under the Accelerated Approval and Priority Review programs.The approval was based on objective response rate (ORR) and duration of response (DOR) data from the FL cohort of a Phase II clinical trial in patients with mutant and wild‑type EZH2.
Overview of Tazverik
Tazverik is an oral, first‑in‑class EZH2 inhibitor.In January 2020, Tazverik received accelerated FDA approval for the treatment of adult and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) who are not candidates for complete resection.
Basis for FL Indication Approval: Phase II Study (NCT01897571)
The new FL indication was supported by data from an open‑label, single‑arm, multicenter Phase II study (Study E7438‑G000‑101, NCT01897571).The study enrolled:
45 patients with FL harboring EZH2 activating mutations
54 patients with FL harboring wild‑type EZH2
Key Efficacy Results (IRC Assessment)
EZH2 mutant cohort:
ORR: 69%
Complete response (CR): 12%
Partial response (PR): 57%
Median duration of response (DOR): 10.9 months
Wild‑type EZH2 cohort:
ORR: 34%
CR: 4%
PR: 30%
Median DOR: 13.0 months
Tazverik demonstrated a favorable safety and tolerability profile in the study.
Confirmatory Trials and Post‑Marketing Commitments
To support full approval of Tazverik for FL, Epizyme is conducting a global, randomized, adaptive trial evaluating Tazverik versus the R2 regimen (Revlimid + Rituxan), an approved chemotherapy‑free immunotherapy, in patients with FL treated in the second‑line or later settings.Approximately 500 FL patients will be enrolled and stratified by EZH2 mutation status. The safety run‑in portion is ongoing.
Epizyme will also fulfill post‑marketing commitments, including expansion of the Phase II trial cohort to enroll wild‑type EZH2 FL patients who have received at least one prior systemic therapy, to support potential future label expansion in the second‑line R/R setting.
Mechanism of Action
The active ingredient of Tazverik is tazemetostat, an oral, potent, first‑in‑class EZH2 inhibitor.EZH2 is a histone methyltransferase. Dysregulated activation of EZH2 leads to aberrant expression of genes controlling cell proliferation, driving uncontrolled growth of non‑Hodgkin lymphoma (NHL) and various solid tumors.Tazemetostat exerts antitumor activity by inhibiting EZH2 enzymatic activity. In clinical studies, tazemetostat showed the ability to safely and effectively reduce or eliminate tumors early in treatment.
Current Clinical Development
Tazemetostat is being investigated in multiple hematologic malignancies and genetically defined solid tumors:
Hematologic malignancies: relapsed or refractory diffuse large B‑cell lymphoma (DLBCL), follicular lymphoma (FL)
Solid tumors: epithelioid sarcoma, synovial sarcoma, INI1‑negative tumors, castration‑resistant prostate cancer, platinum‑resistant solid tumors, etc.
