Taiho Pharmaceutical Submits Application for Approval to Manufacture and Market Novel Antitumor Agent TAS-102

TOKYO, Feb. 27, 2013 /PRNewswire/ -- Taiho Pharmaceutical Co., Ltd. announced on February 27 that it submitted an application on February 26 for approval of the manufacture and marketing of the novel oral nucleoside antitumor agent TAS-102 (combination of trifluorothymidine (FTD) and tipiracil hydrochloride (TPI) ) to the Japanese Ministry of Health, Labor and Welfare. Taiho Pharmaceutical is seeking approval of TAS-102 for the indication of unresectable, advanced, recurrent colorectal cancer.

The application for approval is based on the results of a Phase II clinical trial (Study 10040030) conducted at 20 facilities throughout Japan. It was a randomized, double-blind comparative study of TAS-102 and a placebo involving 172 patients with unresectable, advanced, recurrent colorectal cancer that was refractory to the standard chemotherapy of at least two or more regimens containing fluoropyrimidine, irinotecan, and oxaliplatin. The results indicated that the group administered TAS-102 had improved overall survival rates (median overall survival: 9.0 months vs. 6.6 months) and a significantly reduced risk of mortality (HR: 0.56, p=0.0011). The most frequently reported adverse drug reaction with a CTCAE grade of 3 or higher was neutropenia. Grade 3 or higher diarrhea, fatigue, nausea, and other adverse reactions were no more than 10%. Taiho Pharmaceutical is currently proceeding with a global Phase III clinical trial of TAS-102 in a similar colorectal cancer population (RECOURSE) with the ultimate goal of global registration and commercialization of the agent.

Taiho Pharmaceutical believes that TAS-102 will make a significant contribution to cancer patients and will continue its development efforts to broaden its use.

About TAS-102
TAS-102 is an antitumor agent composed of a combination of trifluorothymidine (FTD), a nucleoside that incorporates into DNA and inhibits a variety of genetic functions required for the proliferation of cancer cells, and tipiracil hydrochloride (TPI), an inhibitor of thymidine phosphorylase (which degrades FTD) that maintains an effective blood concentration of FTD. TAS-102 is administered twice daily to achieve a total daily dose of 70mg/square meter for five days followed by two days of rest and then repeated a second time. This is followed by a 14-day rest period to make a 28-day schedule for one course.

About TAS-102 Phase II Clinical Trial
The Phase II clinical trial was conducted with the participation of 172 patients at 20 medical institutions in Japan from August 2009 to April 2010. The target for the study is an area for which there is currently no fully established therapy in Japan -- specifically, patients refractory to standard chemotherapy for metastatic colorectal cancer who have received at least two or more regimens containing fluoropyrimidine, irinotecan, and oxaliplatin. Patients were randomly assigned TAS-102 (114 cases) or a placebo (58 cases). The primary endpoint was overall survival.

About Global Phase III Clinical Trial (RECOURSE)
The Global Phase III Clinical Trial (RECOURSE) is a randomized, double-blind comparative study of TAS-102 versus a placebo. It is a global Phase III clinical trial that is scheduled to enroll a total of 800 patients from Japan, North America, Europe, and Australia. Patient enrollment began in June 2012. The subjects are patients with unresectable, advanced, recurrent colorectal cancer that is refractory to standard chemotherapies (fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab, and EGFR monoclonal antibody in cases of KRAS wild-type tumor). The trial will compare patients randomly assigned to receive TAS-102 or placebo in order to investigate the efficacy and safety of TAS-102. The primary outcome measure is overall survival. The principal researchers are Dr. Atsushi Otsu, director of the Clinical Development Center of the National Cancer Center Hospital East (Japan), Dr. Robert J. Mayer of the Dana Farber Cancer Institute (USA), and Dr. Eric Van Cutsem of the University Hospital Gasthuisberg (Belgium).

About Taiho Pharmaceutical Co., Ltd.
Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. (http://www.otsuka.com/en/), is an R&D-driven specialty pharma focusing on the three fields of oncology, allergies and immunology, and urology. Its corporate philosophy takes the form of a pledge: "We strive to improve human health and contribute to a society enriched by smiles." In the field of oncology in particular, Taiho Pharmaceutical is known as a leading company in Japan and around the world for developing innovative medicines for the treatment of cancer. In areas other than oncology, as well, the company creates quality products that effectively treat medical conditions and can help improve people's quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer over-the-counter medicinal products that support people's efforts to lead fulfilling and rewarding lives. For more information about Taiho Pharmaceutical, please visit http://www.taiho.co.jp/english/. The company is headquartered in Tokyo and its President is Masayuki Kobayashi.

About Otsuka Holdings Co., Ltd.
The Otsuka Group is a global organization of 156 healthcare companies with nearly 40,000 employees. Otsuka Holdings Co., Ltd., is the Group's holding company. The main operating companies are Otsuka Pharmaceutical Co., Ltd.; Otsuka Pharmaceutical Factory, Inc.; Taiho Pharmaceutical Co., Ltd.; Otsuka Warehouse Co., Ltd.; and Otsuka Chemical Co., Ltd. The Group operates in 25 countries and regions, conducting diversified businesses in four segments, all connected by a focus on health: pharmaceuticals, nutraceuticals, consumer products, and other product areas. The Group's corporate philosophy of "Otsuka people creating new products for better health worldwide" is supported by the corporate ethic of "JISSHO (Proof through Execution) and SOZOSEI (Creativity)." The Otsuka Group thus seeks to foster a culture and vitality appropriate to an enterprise involved with human health and to create innovative products that contribute to the health and wellness of people worldwide. For more information, please visit the company's website at http://www.otsuka.com/en/.

Contact:
Mitsutoshi Utatsu
Public Relations Dept.
Taiho Pharmaceutical Co., Ltd.
Tel: +81-3-3293-2878
e-mail: th-102a@taiho.co.jp
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