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Taiho Pharmaceutical Co., Ltd. today announced that its partner, Servier (France) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending LONSURF^® (trifluridine/tipiracil), as a monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction(GEJ), who have been previously treated with at least two prior systemic treatment regimens for advanced disease.

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The CHMP positive opinion is based on data from a global, randomized Phase III TAGS trial evaluating LONSURF plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated advanced gastric or GEJ adenocarcinoma following progression or intolerance to previous lines of standard therapy. The trial met its primary endpoint demonstrating prolonged overall survival (OS) with trifluridine/tipiracil versus placebo, and a safety profile consistent with prior experience with this drug.¹

CHMP positive opinion will now be reviewed by the European Commission and if marketing authorization is granted, LONSURF will be approved for metastatic gastric cancer in the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein and Norway.

LONSURF is an oral nucleoside antitumor agent discovered and developed by Taiho Pharmaceutical Co., Ltd. In 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialization of LONSURF. Under the terms of the agreement, Servier has been developing and commercializing LONSURF in Europe and other countries outside of the United States, Canada, Mexico and Japan/Asia. In Europe, LONSURF is currently indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

In addition to its indication and use for the treatment for advanced mCRC mainly in Japan, US, and EU, LONSURF obtained approval for additional indication in the US for the treatment for metastatic gastric cancer including adenocarcinoma of the GEJ in February 2019. Application for the same indication has also been filed August 2018 in Japan, and is currently under review by the Japanese health authority.

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

TAGS (TAS-102 Gastric Study) is a Taiho-sponsored, global, randomized, double-blind Phase III study evaluating trifluridine/tipiracil (TAS-102) plus BSC versus placebo plus BSC in patients with metastatic gastric or GEJ cancer, refractory to standard treatments. The primary endpoint in the TAGS trial was OS, and the main secondary endpoint measures included progression-free survival (PFS), safety and tolerability, as well as quality of life.

The TAGS trial aimed to enroll 500 adults 18 years and older, with metastatic gastric or GEJ who had previously received at least two prior regimens for advanced disease. The trial enrolled 507 subjects and was conducted in 17 countries and 110 sites around the world.

The study results were published in The Lancet Oncology

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and colorectal cancer), with an estimated 780,000 deaths annually.² 　

Gastric cancer in Europe affects approximately 130,000 people a year³, and in the last two decades, the proportion of patients with gastric cancer who present with metastases has risen to over 40%.⁴ If diagnosed early, tumors can often be treated by endoscope resection, however in Europe screening is not common place and gastric cancer is diagnosed later.⁵ For those with advanced or metastatic disease the treatment options are limited and are often palliative.

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. Taiho Oncology, Inc., a U.S. subsidiary of Taiho Pharmaceutical, has been marketing LONSURF in the United States for mCRC refractory to prior therapy, since receiving FDA approval in 2015. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TTY Biopharm launched LONSURF in Taiwan in 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of July 2019, LONSURF has been approved as a treatment for advanced mCRC in 68 countries and regions worldwide. In February 2019, LONSURF has been approved as a treatment for metastatic gastric cancer in the United States.

Servier is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes). With a strong international presence in 149 countries and a turnover of 4.2 billion euros in 2018, Servier employs 22,000 people worldwide. Entirely independent, the Group reinvests 25% of its turnover (excluding generics) in research and development and uses all its profits for development. Corporate growth is driven by Servier’s constant search for innovation in five areas of excellence: cardiovascular, immune-inflammatory and neurodegenerative diseases, cancer and diabetes, as well as by its activities in high-quality generic drugs. Servier also offers eHealth solutions beyond drug development.

Becoming a key player in oncology is part of Servier’s long-term strategy. Currently, there are twelve molecular entities in clinical development in this area, targeting gastro-intestinal and lung cancers and other solid tumors, as well as different types of leukemia and lymphomas. This portfolio of innovative cancer treatments is being developed with partners worldwide, and covers different cancer hallmarks and modalities, including cytotoxics, proapoptotics, immune targeted therapies, to deliver life-changing medicines to patients.

Please visit Servier Website for details.
www.servier.com

1. Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2018; 19: 1437–48World Health Organisation.
2. World Health Organization. Globocan (2018), gastric cancer
3. World Health organization. Globacan. World cancer statistics. Available at: https://gco.jarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
4. Bernards N, Creemers GJ, Nieuwenhuijzen GA, et al. No improvement in median survival for patients with metastatic gastric cancer despite increased use of chemotherapy. Ann Oncol. 2013;24:3056–60.
5. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893–907.