OREANDA-NEWS. September 11, 2015. BTG plc (LSE: BTG) announced today that Wellstat Therapeutics' new drug application (NDA) for uridine triacetate has been accepted for review by the United States Food and Drug Administration (FDA). The NDA seeks FDA approval of uridine triacetate as treatment for patients at risk of serious toxicity following an overdose of the chemotherapy agent 5-fluorouracil (5-FU) and patients exhibiting symptoms of serious toxicity within 96 hours of 5-FU administration. Used in combination with other drugs or radiation, 5-FU is a mainstay of chemotherapy across a variety of solid tumors, including those of the colon, stomach, esophagus, breast, pancreas and head and neck.

The FDA has provided an anticipated Prescription Drug User Fee Act (PDUFA) action date in March 2016. Uridine triacetate is being developed by Wellstat Therapeutics. If approved by the FDA, BTG will market, sell and distribute uridine triacetate for this indication in the US. Wellstat Therapeutics retains certain rights to exercise an option to co-promote uridine triacetate. Terms of the co-promote have not been disclosed.

David M. Wohlstadter, Wellstat's Chief Strategy Officer and Counsel, commented: "Our partnership with BTG, which will commercialize this important therapy, demonstrates our shared commitment to the oncology community and cancer patients. This important regulatory milestone brings us one step closer to providing the first and only antidote for patients at risk of serious toxicity following an overdose of 5-fluorouracil (5-FU) and patients exhibiting symptoms of serious toxicity within 96 hours of 5-FU administration."

Carolyn Lewis, BTG's General Manager of Specialty Pharmaceuticals, commented: "Given how common the use of 5-FU is in patients with solid tumors, the negative health and economic impacts of rapid-onset severe toxicity and unintentional overexposure are significant. This filing by Wellstat Therapeutics underscores our shared commitment to bringing an important potential treatment to patients in critical need of care. If granted, FDA approval of uridine triacetate will provide patients and physicians greater access to this novel, potentially life-saving therapy."

Published literature as well as historical data suggest that overexposure to 5-FU can result in serious toxicity or death.

In 2009, uridine triacetate received orphan drug designation from the FDA as an antidote in the treatment of 5-fluorouracil poisoning and from the European Medicines Agency (EMA) as a treatment for 5-fluorouracil overdose. Under an expanded access protocol, FDA emergency treatment provisions in the US, and similar emergency use provisions in Europe and the rest of the world, uridine triacetate is currently provided to patients at risk of excess 5-FU toxicity due to overdose and patients exhibiting serious toxicities to 5-FU within 96 hours of 5-FU administration. The NDA for uridine triacetate is based in part on efficacy and safety data from US sites in this protocol.

5-FU is on the World Health Organization's List of Essential Medicines, a compilation of the most important medications needed in a basic health system. Because 5-FU is administered in different doses and schedules as a frequent component of standard chemotherapy regimens for a variety of cancers, patients can experience dramatically different patterns of toxicity. Overexposure to 5-FU can occur as a result of overdose, genetic variations, impaired clearance or other biochemical factors.

Published literature suggests that each year, approximately 250,000 to 300,000 patients in the US receive multiple treatments with 5-FU, of which 0.5 percent die from 5-FU toxicity. An estimated 10-20 percent of those patients develop serious, sometimes life threatening, 5-FU toxicity or experience an overdose. Non-fatal 5-FU toxicities can result in hospitalization, intensive care utilization and delays in or discontinuation of chemotherapy.