No. 23-26

April 3, 2023
Eisai Co., Ltd.

EISAI ENTERS INTO AGREEMENT WITH NATIONAL CANCER CENTER TOCOLLABORATE ON INVESTIGATOR-INITIATED CLINICAL RESEARCH FOR
ANTICANCER AGENT TAZEMETOSTAT BASED ON “PATIENT-PROPOSEDHEALTHCARE SERVICES” SYSTEM
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has entered into
an agreement with the National Cancer Center to collaborate on investigator-initiated clinical research for
the EZH2 inhibitor tazemetostat hydrobromide (generic name, product name “Tazverik® Tablets 200 mg”,“tazemetostat”) based on “Patient-Proposed Healthcare Services” system. This clinical research will be
conducted by the National Cancer Center Hospital.
The “Patient-Proposed Healthcare Services” system is a system under which medical treatment using
unapproved drugs not covered by insurance is applied for to the government based on the patient's request,
and is conducted as a clinical trial to confirm safety and efficacy. Under the terms of the agreement, Eisai
will provide tazemetostat free of charge to the National Cancer Center Hospital as the drug to be used in“A clinical trial of Tazemetostat for pediatric and AYA* patients with malignant tumors which have nostandard of care or and which is refractory to standard of care: Patients-Proposed Healthcare Service” tobe conducted by the hospital under this program.
Researched and developed by Eisai and Epizyme, Inc.,** an Ipsen (Headquarters: France) company,tazemetostat is a first-in-class, oral small molecule inhibitor of the epigenetic enzyme EZH2. It is one ofthe histone methyltransferases in the epigenetics-related protein group, and is thought to regulate theexpression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2,
which contributes to the cancer growth process.1 Eisai holds the rights for development andcommercialization of tazemetostat in Japan, where it was approved for the indication of “relapsed or
refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is notapplicable)” in 2021, and manufactures and distributes the product.
Eisai positions oncology as a key franchise area and aims to create innovative drugs that act towards
curing cancer. Eisai is committed to expanding the potential clinical benefits of tazemetostat for cancer
treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided
to, patients with cancer, their families and healthcare professionals.
*AYA (Adolescent & Young Adult): Patients between the ages of 15 and 39.

**

Acquired by Ipsen in 2022

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120

[Notes to editors]
1. About the “Patient-Proposed Healthcare Services” system
The “Patient-Proposed Healthcare Services” system is a system that allows patients who wish to use unapproveddrugs and other medications as uninsured treatment to do so promptly, based on the patient's request, while confirming
the safety and efficacy of the drug and allowing access to the unapproved drugs at medical institutions close by. The
objective is to accumulate data and scientific evidence for future insurance coverage.
Ministry of Health, Labour and Welfare “Patient-Proposed Healthcare Services” (Moushide Ryouyou) System:
https://www.mhlw.go.jp/moushideryouyou/ (Japanese only)
2. About tazemetostat hydrobromide (generic name, product name “Tazverik ® Tablets 200 mg”)Tazemetostat is a first-in-class, oral small molecule inhibitor that targets EZH2 that was jointly researched anddeveloped under the alliance agreement between Eisai and Epizyme, Inc., an Ipsen company, utilizing Epizyme, Inc.'s
proprietary product platform. This agent selectively inhibits EZH2 in a competitive matter with S-adenosylmethionine(a methyl group donor) to suppress methylation of H3K27.1 Eisai is responsible for development and commercializationof this agent in Japan, where the drug was approved in June 2021 for the indication of “relapsed or refractory EZH2gene mutation-positive follicular lymphoma (only when standard treatment is not applicable)”. Ipsen is responsible forthe development and commercialization of this agent in the United States, where accelerated approval was granted
for in January 2020 with the indication of “adults and pediatric patients aged 16 years and older with metastatic or
locally advanced epithelioid sarcoma not eligible for complete resection”. In June of the same year, the accelerated
approval was granted for this agent with the indication of “adult relapsed / refractory follicular lymphoma who had atleast 2 regimens of prior treatment and whose tumors are positive for an EZH2 mutation as detected by an FDAapproved test”, and of “adult relapsed / refractory follicular lymphoma for which there are no satisfactory alternativetreatment options”. This agent is not approved outside of Japan and the United States.
3. About epigenetics
Epigenetics is a branch of science that studies the mechanism for the acquired activation/inactivation of gene function
and seeks to determine how gene function is inherited through cell division, irrespective of DNA base sequence
alteration. Examples of modification that lead to the regulation of gene expression include methylation of DNA andmodifications of histone (methylation, acetylation, phosphorylation, etc.).
4. About EZH2
EZH2 is one of the histone methyltransferases within a larger class of epigenetics-related proteins, and specificallycatalyzes the methylation of histone H3 at lysine 27 (H3K27), thus controlling expression of various genes. It isindicated that an increase in methylation of H3K27 caused by EZH2 gain-of-function mutation, overexpression, or thedysfunction of the SWI/SNF (switch/sucrose non-fermenting) complex that reportedly inhibits EZH2 methylation activity,plays an important role in carcinogenesis.11Sarah K. Knutson, Satoshi Kawano, Yukinori Minoshima, et al. Selective Inhibition of EZH2 by EPZ-6438 Leads to Potent Antitumor Activity in EZH2Mutant Non-Hodgkin Lymphoma. Molecular Cancer Therapeutics. 2014 Apr; 13(4):842–854.