Eisai's First-in-Class EZH2 Inhibitor Tazverik Approved in Japan for EZH2 Mutation-Positive Relapsed or Refractory Follicular Lymphoma

Follicular lymphoma (FL, image source: leukemia-cell.org)

June 24, 2021 /BioonBIOON/ -- Eisai recently announced that Japan's Ministry of Health, Labour and Welfare (MHLW) has approved Tazverik (tazemetostat, 200 mg tablets) for the treatment of relapsed or refractoryEZH2For patients with gene mutation-positive follicular lymphoma (FL), this drug is limited to use only when standard therapy is not applicable.

Tazemetostat is an oral, first-in-classEZH2Inhibitor, discovered by Epizyme.This drug is aEpigeneticsDrug, selectively inhibits EZH2, an epigenetic regulator of the histone methyltransferase familyHeredityEnzymes may play an important role in the process of carcinogenesis.Tazemetostat inhibitionEZH2, which can regulate 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 is responsible for all regions outside Japan.

This approval is 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 of other clinical studies conducted by Epizyme outside of Japan. Study 206 enrolledEZH2Patients with relapsed or refractory FL harboring genetic mutations. The primary endpoint is the objective response rate (ORR), and the secondary endpoints include safety.

Study 206 enrolled relapsed or refractoryEZH2Patients with gene mutation-positive primary follicular lymphoma (FL). The results showed that the study met the primary endpoint and exceeded the pre-specifiedTumorResponse threshold, statistically significant: results assessed by the Independent Review Committee (IRC),EZH2The overall response rate (ORR) in mutation-positive relapsed or refractory FL patients (n=17) was 76.5%.(90% CI: 53.9-91.5). The treatment-emergent adverse events (TEAEs; incidence ≥25%) observed in this study included: dysosmia (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%), and increased blood creatine phosphokinase (29.4%).

Eisai will conduct a post-marketing use-results survey (all-case surveillance) for all patients receiving Tazverik until the predetermined number of patients is reached in accordance with the approval conditions stipulated by the MHLW.

Molecular structure of tazemetostat (Image source: Wikipedia)

Follicular lymphoma (FL) is a low-grade B-cell lymphoma that accounts for 10–20% of non-Hodgkin lymphomas (NHL). FL typically grows slowly and is sensitive to chemotherapy. However, due to its frequent relapses, it remains difficult to cure, necessitating the development of new treatment strategies. It has been reported that 7–27% of FL cases harbor gain-of-function mutations in the EZH2 gene. In Japan, approximately 600–2,400 FL patients haveEZH2Mutation.

Tazemetostat is an oral, potent, first-in-class EZH2 inhibitor. EZH2 is a histone methyltransferase that, when aberrantly activated, leads to dysregulation of genes controlling cell proliferation, which can result in uncontrolled rapid proliferation of non-Hodgkin lymphoma (NHL) and various other solid tumor cells. Tazemetostat acts by inhibitingEZH2enzyme activity to exert an antitumor effect. In clinical studies, tazemetostat has demonstrated the ability to safely and effectively shrink or even eliminateTumorability.

In the United States, tazemetostat (brand name: Tazverik) received FDA accelerated approval in January 2020,For the treatment of pediatric and adult patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma (ES) who are not candidates for complete resection.. This approval was based on response rate data from a Phase II clinical study, showing that the overall response rate (ORR) in the ES cohort was 15%, and 67% of patients had a duration of response (DOR) ≥6 months. Notably, tazemetostat is a U.S.FDAThe first approvedEZH2inhibitor, and the first therapy approved by the agency specifically for ES patients, marking a milestone in the clinical treatment of ES.

In June 2020, tazemetostat once again received U.S.FDAAccelerated approval,used for the treatment of two different FL indications: (1) itsTumorViaFDAadult patients with relapsed or refractory (R/R) follicular lymphoma (FL) confirmed as EZH2 mutation-positive by an approved assay and who have previously received at least two systemic therapies; (2) adult patients with R/R FL who have no satisfactory alternative treatment options.This approval is based on Phase IIClinical TrialEZH2-Mutated and Wild-Type Patients in the FL CohortEZH2Data on overall response rate (ORR) and duration of response (DOR) in patients.

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-negativeTumor, castration-resistant prostate cancer, platinum-resistant solid tumors, etc.). (Bioon.com)

Original Source:ANTICANCER AGENT “TAZVERIK® TABLETS 200mg” (TAZEMETOSTAT HYDROBROMIDE) APPROVED IN JAPAN FOR EZH2 GENE MUTATION-POSITIVE FOLLICULAR LYMPHOMA