Taiho Pharmaceutical Co., Ltd. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending Lonsurf (trifluridine/tipiracil), formerly known as TAS-102, 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. Lonsurf is originally developed by Taiho Pharmaceutical, and Servier is the applicant for marketing authorisation of Lonsurf in EU countries under the license agreement with Taiho Pharmaceutical.

The CHMP positive opinion is based on data from the international, double-blind, placebo-controlled phase III RECOURSE study, which investigated the efficacy and safety of Lonsurf with best supportive care (BSC) compared to placebo with BSC in 800 patients with previously treated mCRC. The trial met the primary endpoint of statistically significant improvement in overall survival (OS). Results demonstrated a 32 per cent reduction in risk of death compared to BSC (HR=0.68; 95 per cent CI: 0.58 to 0.81; p<0.001) and an improvement of 1.8 months of median OS (median OS was 7.1 for Lonsurf vs 5.3 months for placebo). The most frequently observed side effects (= 30 per cent) in patients receiving Lonsurf were neutropenia, nausea, fatigue, anemia and leucopenia.

An updated OS analysis in 89 per cent of events, this year presented at ASCO GI, confirmed the clinically meaningful and statistically significant survival benefit of Lonsurf with BSC compared to placebo with BSC. This translates into a 31 per cent relative reduction in the risk of death and an improvement of 2 months in the median OS. The median OS was 7.2 months for Lonsurf with BSC vs 5.2 months for placebo with BSC (HR=0.69; 95 per cent CI: 0.59 to 0.81; p<0.0001), this translated into a 1-year survival rates of 27.1 per cent and 16.6 per cent, respectively.

The CHMP positive opinion will now be reviewed by the European Commission and if marketing authorisation is granted, Lonsurf will be approved in the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein and Norway.

In June 2015, Taiho Pharmaceutical and Servier entered into an exclusive license agreement for the co-development and commercialisation of Lonsurf. Under the terms of the agreement, Servier will commercialise Lonsurf in Europe and other countries outside of the United States, Canada, Mexico and Japan/Asia. Taiho Pharmaceutical retains the right to develop and commercialise Lonsurf in the United States, Canada, Mexico, and Japan/Asia and to manufacture and supply the product.

There remains a high unmet need in the treatment of colorectal cancer (CRC), which was the second leading cause of cancer-related deaths in Europe in 2012, responsible for 215,000 deaths. Approximately 25 per cent of patients with CRC present with metastases at initial diagnosis and almost 50 per cent of patients with CRC will develop metastases. This contributes to the high mortality rates reported for CRC; the 5-year survival rate of patients diagnosed with stage IV mCRC is about 11 per cent.

Lonsurf is currently available in Japan for the treatment of unresectable advanced or recurrent CRC and in the United States 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. Lonsurf is marketed by Taiho Pharmaceutical in Japan and by Taiho Oncology, Inc. a subsidiary of Taiho Pharmaceutical, in the US. Lonsurf is an oral combination anticancer drug of trifluridine (FTD) and tipiracil (TPI), whose primary mechanism of action differs from fluoropyrimidines. 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.