Taiho Pharma Europe Ltd., a subsidiary of Taiho Pharmaceutical, has submitted on February 27, 2015 a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for TAS-102 (trifluridine and tipiracil hydrochloride), an oral combination anticancer drug intended for use in the treatment of refractory metastatic colorectal cancer (mCRC).



This MAA submission closely follows the TAS-102 New Drug Application (NDA) submission to the US Food and Drug Administration (FDA), which was accepted for review by the FDA on February 17, 2015. TAS-102 was approved initially in Japan in March 2014 and launched in May 2014 under the brand name "Lonsurf combination tablet T15, T20".



This MAA submission is supported by the results of the randomized, double blind, placebo controlled, phase III RECOURSE trial of TAS-102 in 800 mCRC patients, whose disease had progressed after or who were intolerant to standard therapies. The TAS-102 RECOURSE trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (HR = 0.68, p < 0.0001) and demonstrated a safety profile consistent with that observed in earlier clinical trials.



TAS-102 is an oral combination investigational 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 2014 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 2014 under the brand name "Lonsurf combination tablet T15, T20".



There are no definitive data on the number of patients who are refractory to standard metastatic colorectal cancer treatments; however, colorectal cancer is one of the most common cancers in the European Unioni and the third most common cancer worldwide. In 2013, a study published in the European Journal of Cancer revealed that an estimated 447,000 patients (242,000 men and 205,000 women) were diagnosed with and 215,000 patients died of colorectal cancer in Europe in 2012.

In addition, the American Cancer Society estimated that 136,830 patients (71,830 men and 65,000 women) were diagnosed with and 50,310 patients died of cancer of the colon and rectum in the US in 2014.