Eisai Submits NDA in Japan for Tazemetostat (Tazverik), a First-in-Class EZH2 Inhibitor, for EZH2 Mutation-Positive Follicular Lymphoma

July 10, 2020 /BioonBIOON/ -- Eisai recently announced that it has submitted a New Drug Application (NDA) to Japanese regulatory authorities, seeking approval for tazemetostat for the treatment ofEZH2Patients with gene mutation-positive follicular lymphoma (FL).

Tazemetostat is an oral, first-in-classEZH2Inhibitor, discovered by Epizyme. This drug is aEpigeneticsDrug, selectively inhibiting EZH2, an epigenetic member of the histone methyltransferase familyGeneticsEnzymes may play an important role in the carcinogenic process. Tazemetostat inhibitsEZH2, which can lead to the control of the expression of various cancer-related genes, thereby inhibiting the proliferation of cancer cells. Eisai is responsible for the development and commercialization of tazemetostat in Japan, while Epizyme, Inc. is responsible for all regions outside of Japan.

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) who are not candidates for complete resection. This approval was based on response rate data from a Phase II clinical study, which showed an overall response rate (ORR) of 15% in the ES cohort, with 67% of responders having a duration of response (DOR) ≥6 months. Notably, tazemetostat is the firstFDAThe first approvedEZH2inhibitor, also the first therapy approved by the agency specifically for ES patients, marking a milestone in the clinical treatment of ES.

This June, tazemetostat received further approval in the United StatesFDAAccelerated approval for the treatment of two different FL indications: (1) itsTumorJingFDAapproved diagnostic test confirmed EZH2 mutation-positive adult patients with relapsed or refractory (R/R) FL who have previously received at least 2 systemic therapies; (2) adult patients with R/R FL who have no satisfactory alternative treatment options. The approval is based on a Phase IIClinical TrialsEZH2-mutant and wild-type patients in the FL cohortEZH2Overall Response Rate (ORR) and Duration of Response (DOR) Data in Patients.

This NDA submission in Japan 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 outside Japan by Epizyme. Study 206 enrolledEZH2Patients with relapsed or refractory FL harboring gene mutations. The primary endpoint was the objective response rate (ORR), and secondary endpoints included safety. Detailed results of this study will be presented at the upcoming academicMeetingpublished above.

The Phase II study conducted by Epizyme enrolled patients with follicular lymphoma (FL) harboring activating EZH2 mutations (n=45) and those with wild-type EZH2 (n=54). As of August 9, 2019, according to the review results from the Independent Review Committee (IRC), in patients with EZH2 mutations and wild-typeEZH2Among the patients, the overall response rates (ORR) for tazemetostat treatment were 69% and 35%, respectively; the median durations of response (DOR) were 11 months and 13 months, respectively; the median progression-free survival (PFS) periods were 14 months and 11 months, respectively; and the median overall survival (OS) was not reached in either group. In this study, tazemetostat demonstrated a favorable safety and tolerability profile.

Molecular Structure of Tazemetostat (Image Source: Wikipedia)

Follicular lymphoma (FL) is a low-grade B-cell lymphoma, accounting for 10-20% of non-Hodgkin lymphoma (NHL). FL typically grows slowly and is sensitive to chemotherapy. However, due to the frequent recurrence of FL, it remains difficult to cure, necessitating the development of new treatment strategies. It has been reported that 7-27% of FL cases have gain-of-function mutations in the EZH2 gene. In Japan, there are approximately 600-2400 FL patients withEZH2Mutation.

Tazemetostat is an oral, potent, first-in-class EZH2 inhibitor. EZH2 is a histone methyltransferase; when abnormally activated, it leads to dysregulation of genes controlling cell proliferation, thereby causing unrestricted and rapid growth of non-Hodgkin lymphoma (NHL) cells and various other solid tumor cells. Tazemetostat acts by inhibitingEZH2enzyme activity, thereby exerting antitumor effects. In clinical studies, tazemetostat demonstrated safe and effective tumor shrinkage or even elimination early in the course of treatment.Tumorability.

Currently, tazemetostat is being developed for the treatment of 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:EISAI SUBMITS MARKETING AUTHORIZATION APPLICATION IN JAPAN FOR ANTICANCER AGENT TAZEMETOSTAT FOR EZH2 GENE MUTATION-POSITIVE FOLLICULAR LYMPHOMA