Tasfygo Tablets 35mg (tasurgratinib succinate) approved in Japan for biliary tract cancer with FGFR2 gene Fusions or rearrangements

In Japan, it has received orphan drug designation from the Ministry of Health, Labour and Welfare (MHLW), and the marketing authorization application was submitted in December 2023.

This approval is based on data such as the results of a multicenter, open-label, single-arm clinical phase II trial (Study 201) conducted by Eisai in Japan and China. Study 201 enrolled 63 patients with unresectable advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions or rearrangements previously treated with gemcitabine-based combination chemotherapy. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety. This study achieved its primary endpoint and exceeded a prespecified tumor response threshold (15%) with statistical significance: ORR of patients treated with Tasfygo was 30.2% (90% confidence interval (CI): 20.7-41.0) as assessed by independent imaging review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were hyperphosphataemia (81.0%), palmar-plantar erythrodysaesthesia syndrome (44.4%), diarrhoea (36.5%), aspartate aminotransferase increase (31.7%), alanine aminotransferase increase (28.6%) and stomatitis (25.4%).

The estimated number of patients in Japan with biliary tract cancer is approximately 22,000, with approximately 25% of the five-year relative survival rate, making it an intractable cancer with the second worst prognosis following pancreatic cancer. Since drug therapy options are limited in comparison with other cancers, it is a disease with significant unmet medical needs. FGFR2 gene fusions or rearrangements are observed in approximately 14% of intrahepatic cholangiocarcinoma, which accounts for 15-30% of biliary tract cancers.

FGFR genetic aberrations such as the gene fusions are known to be deeply involved in the proliferation, survival and migration of cancer cells as well as tumor angiogenesis and drug resistance. As these genetic aberrations in FGFRs have been observed in various other types of cancers as well as biliary tract cancer, there is growing interest in FGFRs as a promising target for cancer therapy. Tasfygo is thought to show tumor growth inhibition by selectively inhibiting FGFR1, 2 and 3, and blocking those signals. In non-clinical studies, the antitumor activity of Tasfygo was confirmed in cells expressing the FGFR2-fusion genes, which were identified by the National Cancer Center Japan  through large-scale genomic analysis of Japanese biliary tract cancer. The companion diagnostic test to detect FGFR2 gene fusions or rearrangements for the use of Tasfygo in biliary tract cancer, “AmoyDx® FGFR2 Break-apart FISH Probe Kit” by Nihon Stery, Inc.  was approved in August 2024.