NEWS RELEASE
August 23, 2017
Nippon Shinyaku Co.,Ltd.
Chugai Pharmaceutical Co.,Ltd.

New Drug Application Filed for
Glycoengineered Type II Anti-CD20 Monoclonal Antibody, Obinutuzumab
August 23, 2017 -- Nippon Shinyaku Co., Ltd. (TOKYO: 4516) and Chugai Pharmaceutical Co., Ltd.
(TOKYO: 4519) announced today that Chugai filed a new drug application to the Ministry of Health,Labour and Welfare (MHLW), for glycoengineered type II anti-CD20 monoclonal antibody,obinutuzumab (genetical recombination) which was co-developed by the two companies for thetreatment of “CD20-positive B-cell follicular lymphoma (FL)” in Japan.
Dr. Kazuya Mori, Nippon Shinyaku's Corporate Officer, Head of R&D Administration Div. said "I
am very glad that a new drug application for our co-developed product, obinutuzumab, was filed. By
adding this new product to our lineup in the area of hematologic malignancies, on which we arefocusing, we will make utmost efforts to meet the demands of the clinical setting and contribute to
the treatment of patients.""Combination therapy of rituximab and chemotherapy has been used as the standard treatment forCD20-positive B-cell FL for a long time. As a new treatment option, Obinutuzumab was confirmed tobe more beneficial than the conventional treatment with rituximab for the treatment of FL," said Dr.
Yasushi Ito, Chugai’s Senior Vice President, Head of Project & Lifecycle Management Unit. "We arecommitted to deliver obinutuzumab to patients as early as possible to contribute to the access tobetter treatments in Japan."This filing was based on the results of the GALLIUM study, a global phase III clinical study
conducted by Roche and participating from Japan and other several clinical studies.
The GALLIUM study is a global Phase III open-label, multi-center, randomized two-arm study that
evaluated the efficacy and safety of obinutuzumab plus chemotherapy followed by obinutuzumabalone (obinutuzumab arm) compared with rituximab plus chemotherapy followed by rituximab alone(rituximab arm) in 1,401 patients with previously untreated CD20-positive advanced non-Hodgkin’slymphoma. The primary endpoint of the study was investigator-assessed progression free survival(PFS) in 1,202 patients with FL. The secondary endpoints were PFS assessed by an independent
review committee (IRC), overall survival (OS), safety, and other endpoints.
With respect to the primary endpoint, as the median PFS was not reached, the results showed that

obinutuzumab arm reduced the risk of disease progression, recurrence or death in patients with FL
by 34% (HR=0.66, 95% CI: 0.51-0.85, p=0.0012, stratified log-rank test, Data cut-off: January 31,2016) compared to rituximab arm. Concerning secondary endpoints, the median PFS assessed by theIRC was not reached as well, the risk of disease progression, recurrence or deaths decreased by 29%(HR=0.71, 95% CI: 0.54-0.93, p=0.0138, stratified log-rank test, Data cut-off: January 31, 2016). The
median OS did not reach in both arms due to small numbers of events. As for safety, the adverse
events (AEs) expressed in both arms in the GALLIUM study were consistent with previous reports.
The Grade 3 or higher AEs which was observed in 5% or more frequently for obinutuzumab arm thanrituximab arm was neutropenia (43.9% for obinutuzumab arm vs. 37.9% for rituximab arm).
Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody designed to attach toCD20, a protein expressed on certain B cells, but not on stem cells or plasma cells, same as rituximab
which is recommended as a treatment of non-Hodgkin’s lymphoma in treatment guidelines in Japanand overseas. Obinutuzumab is designed to attack and destroy targeted B-cells both directly andtogether with the body's immune system.
In Japan, the prevalence of malignant lymphoma was reported to be approximately 27,000 and thenumber of deaths due to the disease was reported to be approximately 11,000 in 2012 1, 2). Since thecases of Hodgkin's lymphoma is reported to account for approximately 8 to 10% of the cases ofmalignant lymphoma in Japan3), the prevalence of non-Hodgkin's lymphoma is estimated to beapproximately 24,000 and the number of deaths from this condition is estimated to be approximately
10,000. The prevalence of and deaths from malignant lymphoma tend to increase in recent years1, 2),and a same tendency is seen in patients with non-Hodgkin's lymphoma.
Nippon Shinyaku and Chugai will work for the early approval to provide obinutuzumab as a newtreatment option for patients with CD20-positive B-cell follicular lymphoma and medical
professionals.
1. Center for Cancer Control and Information Services, National Cancer Center. National estimatesof cancer incidence based on cancer registries in Japan (1975-2012) (http://ganjoho.jp/en/)
2. Center for Cancer Control and Information Services, National Cancer Center. Cancer mortality
from Vital Statistics in Japan (1958-2015) (http://ganjoho.jp/en/)
3. Japanese Society of Hematology. Guidelines on Treatment of Hematopoietic Tumors (2013) Version
1.2. (http://www.jshem.or.jp/gui-hemali/table.html, Japanese only)

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Nippon Shinyaku Co., Ltd.

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