Eisai Launches Tazverik (Tazemetostat), a First-in-Class EZH2 Inhibitor, in Japan for EZH2 Mutation-Positive Relapsed or Refractory Follicular Lymphoma

Eisai recently announced the launch of the anticancer drug Tazverik in the Japanese market, indicated for the treatment of patients with relapsed or refractory EZH2 mutation-positive follicular lymphoma.

Eisai recently announced that it has launched the anticancer drug Tazverik (tazemetostat, 200 mg tablets) in the Japanese market, with an indication for the treatment of patients with relapsed or refractory EZH2 mutation-positive follicular lymphoma (FL) (for use only when standard therapy is not applicable).

The active pharmaceutical ingredient of Tazverik is tazemetostat, an oral, first-in-class small-molecule EZH2 inhibitor developed utilizing the proprietary platform of Epizyme, Inc. It is an epigenetic drug that selectively inhibits EZH2. EZH2 is an epigenetic enzyme belonging to the histone methyltransferase family and is believed to play a critical role in oncogenesis. Inhibition of EZH2 by tazemetostat modulates the expression of various cancer-related genes, thereby inhibiting cancer cell proliferation. Eisai is responsible for the development and commercialization of tazemetostat in Japan, while Epizyme, Inc. is responsible for all regions outside Japan.

In Japan, Tazverik was approved in June 2021. The approval was based on the results of a multicenter, open-label, single-arm Phase II clinical trial (Study 206) conducted by Eisai in Japan, as well as the results from other clinical studies conducted by Epizyme outside of Japan. Study 206 enrolled patients with relapsed or refractory primary follicular lymphoma (FL) positive for EZH2 mutations. The primary endpoint was objective response rate (ORR), and secondary endpoints included safety.

The results showed that Study 206 met its primary endpoint and exceeded the prespecified tumor response threshold with statistical significance: based on the Independent Review Committee (IRC) assessment, the overall response rate (ORR) in patients with EZH2 mutation-positive relapsed or refractory follicular lymphoma (FL) (n=17) was 76.5% (90% CI: 53.9–91.5). Treatment-emergent adverse events (TEAEs) with an incidence ≥25% observed in the study included: olfactory dysfunction (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%), and increased blood creatine phosphokinase (29.4%).

Eisai will conduct a post-marketing surveillance (all-case surveillance) on all patients treated with Tazverik until the predetermined number of patients is reached, in accordance with the approval conditions stipulated by the MHLW.

Follicular lymphoma (FL) is a low-grade B-cell lymphoma that accounts for 10–20% of non-Hodgkin lymphoma (NHL). FL typically exhibits indolent growth and is responsive to chemotherapy. However, due to its propensity for frequent relapse, it remains difficult to cure, necessitating the development of novel therapeutic strategies. It has been reported that 7–27% of FL cases harbor gain-of-function mutations in the EZH2 gene. In Japan, approximately 600 to 2,400 FL patients are estimated to carry EZH2 mutations. In May 2021, Roche Diagnostics K.K.'s cobas EZH2 Mutation Test was approved as a companion diagnostic assay for EZH2 gene mutations.

Tazemetostat is an oral, potent, first-in-class EZH2 inhibitor. EZH2 is a histone methyltransferase; when aberrantly activated, it leads to the dysregulation of genes controlling cell proliferation, thereby causing the uncontrolled and rapid growth of non-Hodgkin lymphoma (NHL) and various other solid tumor cells. Tazemetostat exerts its antitumor effects by inhibiting EZH2 enzymatic activity. In clinical studies, tazemetostat has demonstrated the ability to safely and effectively shrink or even eliminate tumors early in the course of treatment.

In the United States, tazemetostat (brand name: Tazverik) received accelerated approval from the FDA in January 2020 for the treatment of pediatric and adult patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) that is not amenable to complete resection. This approval was based on response rate data from a Phase II clinical study, which demonstrated an overall response rate (ORR) of 15% in the ES cohort, with 67% of patients achieving a duration of response (DOR) of ≥6 months. Notably, tazemetostat is the first EZH2 inhibitor approved by the U.S. FDA and the first therapy approved by the agency specifically for patients with ES, marking a milestone in the clinical treatment of ES.

In June 2020, tazemetostat received accelerated approval from the U.S. FDA for the treatment of two distinct FL indications: (1) adult patients with relapsed or refractory (R/R) FL whose tumors are confirmed to be EZH2 mutation-positive by an FDA-approved test and who have received at least two prior systemic therapies; (2) adult patients with R/R FL who have no satisfactory alternative treatment options. This approval was based on overall response rate (ORR) and duration of response (DOR) data from EZH2 mutation-positive and wild-type EZH2 patients in the FL cohort of a Phase II clinical trial.

Currently, tazemetostat is being developed for various types of hematologic malignancies (non-Hodgkin lymphoma: relapsed or refractory diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and genetically defined solid tumors (epithelioid sarcoma, synovial sarcoma, INI1-negative tumors, castration-resistant prostate cancer, platinum-resistant solid tumors, etc.).

Source: Anticancer Agent "Tazverik Tablets 200mg" (Tazemetostat Hydrobromide) Launched in Japan for EZH2 Gene Mutation-Positive Follicular Lymphoma

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