Taiho Oncology, Inc. announced the FDA has accepted and granted priority review for the supplemental New Drug Application 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 action date of February 24, 2019.
The sNDA is based on data from the global, randomized, double blind pivotal phase III trial evaluating LONSURF versus placebo and best supportive care in patients with heavily pretreated metastatic gastric/gastroesophageal junction adenocarcinoma that progressed or were intolerant to previous lines of therapy.
The trial met its primary endpoint of prolonged overall survival and secondary endpoint measures of progression-free survival as well as continuing to demonstrate LONSURF’s consistent safety and tolerability profile.
Full results from this study were recently presented at the European Society of Medical Oncology 2018 Congress in Munich and published simultaneously in The Lancet Oncology.
Lonsurf, in the U.S., is indicated for the treatment of patients with metastatic colorectal cancer 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.
TAGS (TAS-102 Gastric Study) is a Taiho-sponsored pivotal phase III, multinational, randomized, double-blind study evaluating trifluridine/tipiracil, also known as TAS-102, plus best supportive care 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, and the main secondary endpoint measures include progression-free survival, and safety and tolerability, as well as quality of life.
TAGS enrolled 507 adult patients with metastatic gastric cancer who had previously received at least two prior regimens for advanced disease. The study was conducted in Japan, the United States, the European Union, Russia, Belarus, Israel, and Turkey.
Standard chemotherapy regimens for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. The addition of trastuzumab to chemotherapy is standard of care for patients with HER2-neu-positive advanced gastric cancer. However, after failure of first- and second-line therapies, standard third-line treatments are limited.
Lonsurf (trifluridine/tipiracil) is an oral anticancer drug, which utilizes the combination of trifluridine and tipiracil, 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 June 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 TYY 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.
Lonsurf is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of patients with metastatic colorectal cancer 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.
