Approval Announcement
Eisai recently announced that Japan has approved the anticancer drug Tazverik (tazemetostat, 200 mg tablets) for the treatment of patients with relapsed or refractory EZH2 mutation‑positive follicular lymphoma (FL), limited to cases where standard therapy is not applicable.
Mechanism of Action of Tazverik
The active ingredient of Tazverik is tazemetostat, an oral, first‑in‑class small molecule inhibitor of EZH2, discovered using Epizyme’s proprietary platform.As an epigenetic therapeutic agent, it selectively inhibits EZH2, a histone methyltransferase and epigenetic enzyme that plays a critical role in oncogenesis.Inhibition of EZH2 by tazemetostat regulates the expression of various cancer‑related genes and suppresses cancer cell proliferation.
Results of Phase 2 Trial (Study 206)
Tazverik was approved in Japan in June 2021, based on results from a multicenter, open‑label, single‑arm Phase 2 clinical trial (Study 206) conducted in Japan, plus other overseas clinical studies by Epizyme.
Study Design
Enrolled patients with EZH2 mutation‑positive relapsed or refractory primary follicular lymphoma (FL).
Primary endpoint: objective response rate (ORR).
Secondary endpoint: safety.
Key Efficacy Results
The study met its primary endpoint with statistically significant tumor response exceeding the predefined threshold.
By independent review committee (IRC) assessment:
ORR in EZH2 mutation‑positive relapsed or refractory FL patients (n=17): 76.5% (90% CI: 53.9–91.5).
Common Treatment‑Emergent Adverse Events (TEAE ≥ 25%)
Dysosmia (52.9%)
Nasopharyngitis (35.3%)
Lymphopenia (29.4%)
Blood creatine phosphokinase increased (29.4%)
Post‑Marketing Commitment
Eisai will conduct a post‑marketing all‑case surveillance for all patients treated with Tazverik until the required patient enrollment number is reached under the approval conditions specified by the Ministry of Health, Labour and Welfare (MHLW).
Global Approvals of Tazemetostat (Tazverik)
US FDA Approvals
January 2020
Accelerated approval for adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) who are not candidates for complete resection.
ORR in ES cohort: 15%; 67% of responders had duration of response (DOR) ≥ 6 months.
Tazemetostat became the first FDA‑approved EZH2 inhibitor and the first therapy specifically approved for ES.
June 2020
Accelerated approval for two indications in relapsed or refractory (R/R) FL:
Approval based on ORR and DOR data from Phase 2 trial in FL patients with mutant or wild‑type EZH2.
Adult patients with EZH2 mutation‑positive R/R FL who have received at least two prior systemic therapies.
Adult patients with R/R FL for whom no satisfactory alternative treatment exists.
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.
