- TAS-102 Demonstrated Statistically Significant Improvement in Overall Survival and Progression-free Survival -

- Study Findings form Foundation for Regulatory Submissions in U.S. and Europe -

Taiho Pharmaceutical Co., Ltd. announced on June 30 detailed findings from its global Phase III RECOURSE trial of TAS-102 (nonproprietary names: trifluridine and tipiracil hydrochloride, brand name in Japan "Lonsurf (R) combination tablet T15, T20"), an oral combination anticancer drug. TAS-102 achieved statistically significant improvements in overall survival (OS, primary efficacy endpoint) and progression-free survival (PFS) in patients with refractory metastatic colorectal cancer (mCRC) whose disease had progressed after or who were intolerant to standard therapies. TAS-102 demonstrated a safety profile consistent with that observed in earlier clinical trials. The TAS-102 data were presented on Saturday, June 28 during an oral presentation at the European Society for Medical Oncology (ESMO) 16th World Congress on Gastrointestinal Cancer in Barcelona, Spain.

The TAS-102 RECOURSE trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (HR = 0.68, p less than 0.0001).TAS-102 reduced the risk of mortality by 32% when compared to placebo. Median overall survival was 7.1 months (95% CI: 6.5-7.8) and 5.3 months (95% CI: 4.6-6.0) for TAS-102 and placebo, respectively, and was improved in favor of TAS-102 by 1.8 months. There was also a statistically significant 52% decrease in the risk of disease progression between the two arms (HR = 0.48, p less than 0.0001). In addition, the disease control rate of patients treated with TAS-102 was 44.0% versus 16.3% for patients treated with placebo (p less than 0.0001). These results were consistent across study regions.

"The RECOURSE results suggest the efficacy of TAS-102 as a new treatment option for patients with mCRC," said Dr. Atsushi Ohtsu, one of the principal researchers of this study and the Director of the Exploratory Oncology Research & Clinical Trial Center of the National Cancer Center, Japan.   

The most commonly reported adverse events included hematological (anemia, neutropenia, and leukopenia) and gastrointestinal (diarrhea, nausea, and vomiting) events. Laboratory grade III/IV neutropenia in TAS-102 vs placebo was 37.9% vs 0%, anemia was 18.2% vs 3.0%, and thrombocytopenia was 5.1% vs 0.4%. Febrile neutropenia was 3.8% vs 0%. Grade III/IV diarrhea was 3.0% vs 0.4%, vomiting was 2.1% vs 0.4%, nausea was 1.9% vs 1.1%, fatigue was 3.9% vs 5.7%, and stomatitis was 0.4% vs 0%.

Taiho plans to submit NDA in the U.S. at the end of 2014 and MAA in Europe in the first quarter of 2015.  

About The RECOURSE Study

The RECOURSE trial was a global, randomized, double-blind, placebo-controlled Phase III comparison trial evaluating the efficacy and safety of orally administered TAS-102 in patients with refractory mCRC. The trial enrolled 800 patients in North America, Japan, Europe and Australia who received at least two prior regimens of standard chemotherapies for mCRC and were refractory to, or failed, those chemotherapies. Patients were randomized (2:1) to receive TAS-102 (35 mg/square meter) or placebo, plus best supportive care, twice daily. The primary objective of the RECOURSE trial was improvement in overall survival (OS) versus placebo.

The principal investigators are Dr. Atsushi Ohtsu of the National Cancer Center (Japan), Dr. Robert J. Mayer of the Dana Farber Cancer Institute (USA) and Dr. Eric Van Cutsem of the University Hospitals Leuven (Belgium).

About Metastatic Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide. In 2014, it is estimated that 136,830 patients (71,830 men and 65,000 women) will be diagnosed with, and 50,310 patients will die of, cancer of the colon or rectum in the United States (*1). Colorectal cancer was the second most common cancer in Europe in 2012. In addition, it was estimated that 447,000 patients (242,000 men and 205,000 women) were diagnosed with and 215,000 patients died of colorectal cancer in Europe during 2012 (*2).

About TAS-102

TAS-102 is an oral combination anticancer drug of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is an antineoplastic nucleoside analog, which is incorporated directly into DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase. TAS-102 was approved initially in Japan in March this year for the indications of "unresectable advanced or recurrent colorectal cancer (only if refractory to standard therapies)," based on the results of the Phase II clinical trial conducted in Japan, and launched in Japan in May under the brand name "Lonsurf (R) combination tablet T15, T20".

About Taiho Pharmaceutical Co., Ltd.

Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd., 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.

Headquarters: Tokyo

President: Masayuki Kobayashi

For more information about Taiho Pharmaceutical, please visit

http://www.taiho.co.jp/english/.

About Otsuka Holdings Co., Ltd.

The Otsuka Group is a global organization of 166 healthcare companies with nearly 44,000 employees. Otsuka Holdings Co., Ltd. is the Group's holding company. The Group operates in 26 countries and regions, conducting diversified businesses in four segments all connected by a focus on health: pharmaceuticals, nutraceuticals, consumer products, and others.

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/.

References

(*1) Cancer facts & figures 2014. American Cancer Society.

(*2) Ferlay, J. et. al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer. 49; 1374-1403.