July 28, 2019/
BioValleyBIOON/--French pharmaceutical company Servier and its partner Taiho Pharmaceutical recently jointly announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Lonsurf (trifluridine/tipiracil) for the treatment of adult patients with metastatic gastric cancer (mGC) (including metastatic gastroesophageal junction adenocarcinoma [mGEJC]) whose advanced disease has been previously controlled by at least two systemic therapy regimens.
In Europe, gastric cancer affects approximately 130,000 people annually, with an estimated 40% of patients developing metastatic disease. For patients with advanced or metastatic disease, treatment options are limited and typically consist of palliative care. The Committee for Medicinal Products for Human Use (CHMP) opinion will now be submitted to the European Commission (EC), which will consider the CHMP’s recommendation and issue a final decision within the next two to three months. In the European Union, the current indication for Lonsurf is for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have previously been treated with, or are not suitable for, currently available therapies, including chemotherapy regimens containing fluoropyrimidines, oxaliplatin, and irinotecan, as well as anti-VEGF and anti-EGFR agents.
In terms of U.S. regulatory affairs, Lonsurf was approved at the end of February this year
FDAApproved for the treatment of adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma who have previously received at least two prior chemotherapy regimens (including fluoropyrimidine, platinum, and either a taxane or irinotecan; and HER2/neu-targeted therapy, if applicable). This approval expands the U.S. indications for Lonsurf, which was previously approved for patients with metastatic colorectal cancer (mCRC) who have been treated with standard chemotherapy.
The Marketing Authorization Application (MAA) for Lonsurf in the European Union was based on data from the global Phase III clinical study TAGS (TAS-102 Gastric Study). This randomized, double-blind study evaluated the efficacy and safety of Lonsurf plus best supportive care (BSC) versus placebo plus BSC in patients with metastatic gastric cancer refractory to standard therapies. The results demonstrated that the study met both its primary and secondary endpoints: in the overall study population, Lonsurf plus BSC achieved a clinically and statistically significant improvement in overall survival (OS) compared to placebo plus BSC, reducing the risk of death by 31% (HR=0.69 [95% CI: 0.56–0.85], p=0.00029) and extending median OS by 2.1 months (5.7 months vs. 3.6 months). The overall safety profile was consistent with that observed in Lonsurf-treated patients with metastatic colorectal cancer (mCRC), with hematologic adverse events being the most commonly reported. The full results of the TAGS study were presented at the 2018 European Society for Medical Oncology (ESMO) Congress and published in The Lancet.
Tumor(The Lancet Oncology).
In mid-January this year, Dapeng Pharmaceutical at the 2019 American Clinical
TumorEfficacy and safety data for the gastrectomy subgroup in the TAGS study were presented at the ASCO-GI Symposium on Gastrointestinal Cancers. These results were consistent with those observed in the overall study population. In the TAGS study, 221 (44%) of the 507 randomized patients with metastatic gastric cancer (mGC) had previously undergone gastrectomy (147 received Lonsurf and 74 received placebo), reflecting
Diagnosisin the real-world patient population with mGC. The results showed that in this patient subgroup, Lonsurf prolonged overall survival compared with placebo, regardless of prior gastrectomy.
Director of the Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital
TumorProfessor Josep Tabernero, Department Chair, stated: “The CHMP’s positive opinion on Lonsurf is highly welcome; treatment options for patients with metastatic gastric cancer remain limited, making it paramount to provide new therapeutic approaches. Data from the phase III TAGS study demonstrate that Lonsurf is effective and well tolerated in these patients, granting them precious additional months of life.”
Servier
TumorPatrick Therase, Head of R&D, stated, “Today’s announcement brings us one step closer to ensuring that patients with metastatic gastric cancer have another treatment option offering higher survival rates than standard therapy. Gastric cancer is difficult to treat, and every step forward represents a significant advance.”
Lonsurf is a novel oral antimetabolite combination drug, consisting of anti-
TumorIt consists of the nucleoside analog FTD (trifluridine) and the thymidine phosphorylase inhibitor TPI (tipiracil). FTD can directly incorporate into the DNA double helix by replacing thymine during DNA replication, leading to DNA dysfunction and interfering with cancer cell DNA synthesis; TPI inhibits thymidine phosphorylase, which is involved in FTD degradation, thereby reducing FTD breakdown and maintaining its plasma concentration.
As of July 2019, Lonsurf had been approved in 68 countries worldwide for the treatment of patients with metastatic colorectal cancer (mCRC), specifically adult patients with mCRC who had previously been treated with, or were not candidates for, available therapies (including fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy, anti-VEGF agents, and anti-EGFR agents). In February 2019, Lonsurf received approval in the United States for a new indication: the treatment of adult patients with metastatic gastric cancer (mGC) or metastatic gastroesophageal junction adenocarcinoma (mGEJC).
Lonsurf was discovered and developed by Taiho Pharmaceutical. In June 2015, Servier and Taiho Pharmaceutical entered into an exclusive licensing agreement to jointly develop and commercialize Lonsurf in Europe, the United States, Canada, Mexico, and other countries outside Asia. (Bioon.com)
