FDA approves Vistogard (uridine triacetate) as antidote to 5-fluorouracil- Wellstat Therapeutics

The FDA has approved Vistogard (uridine triacetate), from Wellstat Therapeutics, as the first and only antidote for emergency treatment of adult and paediatric patients following an overdose of the chemotherapy agents 5-fluorouracil (5-FU) or capecitabine regardless of the presence of symptoms, or to treat patients who exhibit early-onset, severe or life-threatening toxicity affecting cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions within 96 hours after the end of treatment with 5-FU or capecitabine.

The FDA approval of Vistogard is based on data from a development programme in 135 patients designed to demonstrate the efficacy and safety of a single course of 10 grams given orally every six hours for a total of 20 doses (patients in the studies had either received an overdose of 5-FU or capecitabine, or presented with severe or life-threatening toxicities within 96 hours following the end of 5-FU or capecitabine administration). In clinical studies, overall survival of patients with 5-FU toxicity receiving Vistogard was 96%, compared with 16% in historical cases employing standard supportive care measures. Vistogard also helped patients resume chemotherapy sooner, with 33% resuming their cancer treatment within 30 days. Adverse events that occurred in >2% of patients were vomiting (10%), nausea (5%) and diarrhoea (3%).

Comment: 5-FU and capecitabine are essential components of combination anticancer regimens that include other chemotherapy agents or radiation to treat solid tumours including those of the colon, stomach, pancreas, breast, head and neck. It is estimated that 10–20% of patients treated with 5-FU or capecitabine develop severe or life-threatening toxicity or experience an overdose, and that approximately 0.5% of patients die from such toxicity.