News Releases

Taiho Pharmaceutical Co., Ltd. today announced that the United States Food and Drug Administration (FDA) has accepted and granted priority review for the supplemental New Drug Application (sNDA) submitted by its U.S. subsidiary Taiho Oncology, Inc. for LONSURF^® (trifluridine/tipiracil, TAS-102) as a treatment for patients with previously treated, advanced or metastatic gastric adenocarcinoma, including cancer of the gastroesophageal junction. The FDA has provided an anticipated Prescription Drug User Fee Act (PDUFA) action date of February 24, 2019.

The sNDA is based on data from the global, randomized, double blind pivotal Phase III (TAGS) trial evaluating LONSURF versus placebo and best supportive care in patients with pretreated metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma that progressed or were intolerant to previous lines of therapy. The trial met its primary endpoint of prolonged overall survival (OS) and secondary endpoint measures of progression-free survival (PFS) consistently supported the OS results, as well as continuing to demonstrate LONSURF’s consistent safety and tolerability profile. Full results from this study were presented on October 21 as an oral presentation at ESMO 2018 Congress in Munich and published simultaneously in The Lancet Oncology.

Taiho remains committed to making further contributions to patients and to medical practitioners engaged in the treatment of cancer.

The TAGS (TAS-102 Gastric Study) trial is a Taiho-sponsored pivotal Phase III multinational, randomized, double-blind study evaluating LONSURF^® (trifluridine/tipiracil), also known as TAS-102, plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic gastric cancer, including gastroesophageal junction cancer, refractory to standard treatments. The primary endpoint in the TAGS trial is overall survival (OS), and the main secondary endpoint measures include progression-free survival (PFS), and safety and tolerability, as well as quality of life.

The TAGS trial aimed to enroll 500 adults 18 years and older, with metastatic gastric cancer who had previously received at least two prior regimens for advanced disease. The trial enrolled 507 subjects and was conducted in Japan, the United States, the European Union, Russia, Belarus, Israel, and Turkey.

For more information on the TAGS trial, please visit
www.ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02500043).
The ClinicalTrials.gov Identifier is NCT02500043.

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and liver cancer), with an estimated 723,000 deaths annually¹. In Japan, gastric cancer is the most common cancer and the third most common cause of cancer-related death (after lung and colorectal cancer), causing around 45,000 deaths annually².

In recent years, the outcome for gastric cancer has improved remarkably, and survival has increased dramatically over the past 10 years. As cancer progresses, however, numerous complications can limit the usable drugs and preclude intensive chemotherapy. Prolonging survival and relieving symptoms in late-stage treatment for metastatic gastric cancer are issues for which it is thought important to increase the options for new therapeutic drugs. At present, nivolumab and irinotecan are recommended in Japan as the standard third line treatment for metastatic gastric cancer.

LONSURF (trifluridine/tipiracil) is an oral anticancer drug, which utilizes the combination of trifluridine (FTD) and tipiracil (TPI), whose dual mechanism of action is designed to maintain clinical activity and differs from conventional fluoropyrimidines. FTD is an antineoplastic nucleoside analogue, which is incorporated directly into the 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.

In Japan, Taiho Pharmaceutical has been marketing LONSURF for the treatment of unresectable advanced or recurrent colorectal cancer since 2014. In the United States, beginning in 2015, Taiho Oncology, Inc., a U.S. subsidiary of Taiho Pharmaceutical, began marketing the drug for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Asia. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TTY Biopharm launched LONSURF in Taiwan in July 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of October 2018, LONSURF has been approved as a treatment for advanced mCRC in 61 countries and regions worldwide.

1. Ferlay J, Soerjomataram I, Dikshit R, et al. Int J Cancer. 2015;136:E359-86.
2. “Latest Cancer Statistics,” a cancer information service of the National Cancer Center Japan (in Japanese).
   https://ganjoho.jp/reg_stat/statistics/stat/summary.html Last accessed October 2018