The FDA's decision was based on two studies that measured the 30-day survival rate of adult and pediatric patients who had either overdosed on treatment or were experiencing early-onset toxicities.
The FDA has approved Vistogard (uridine triacetate) for the emergency treatment of adult and pediatric patients who had severe or life-threatening toxicities within four days of treatment following an overdose of 5-fluorouracil (5-FU) or capecitabine.
The FDA's decision was based on two, open-label clinical studies that measured the 30-day survival rate of adult and pediatric patients who had either overdosed on treatment or were experiencing early-onset toxicities. Of those who overdosed, 97 percent treated with Vistogard were still alive after 30 days. Of those treated for toxicities, 89 percent were alive at 30 days.
The approval marks the first emergency antidote for specific chemotherapies.
“Treating cancer requires not only selecting which drug may be most effective and well tolerated, but ensuring the correct dose is given at proper intervals. While rare, unintentional overdose can occur,” Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“Today's approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents.”
Developed by Wellstat Therapeutics, the oral agent Vistogard blocks cell damage and death caused by 5-FU and should be taken soon after overexposure — regardless of whether symptoms are present—or early onset of severe toxicities, including severe mucositis, fever, diarrhea, or rash.
Vistogard was tested on 135 adult and pediatric patients in two separate trials who had either overdosed on 5-FU or capecitabine or experienced unusual, life-threatening adverse events within 4 days of receiving 5-FU infusion therapy. The FDA noted that the agent’s safety and efficacy has not been evaluated when treatment is initiated more than 96 hours following chemotherapy administration.
The study measured overall survival at 30 days after taking Vistogard, as well as resumption of chemotherapy within the 30 days.
In addition to a 97 percent survival rate in the overdose group and 89% in the toxicity group, both trials showed that 33 percent of patients resumed chemotherapy within 30 days of being treated with Vistogard.
The agent’s approval is for emergency reactions only following 5-FU or capecitabine, because it can lessen the efficacy of the drugs in non-emergent situations.
Adverse events occurring in more than 2 percent of patients receiving Vistogard included vomiting (10 percent), nausea (5 percent) and diarrhea (3 percent).
The FDA had granted Vistogard priority review and fast track designations to expedite the review and approval of the drug. It has now been granted orphan drug designation, which is intended to expedite the development of the drug by providing incentives such as clinical trial tax credits, user fee waivers, and eligibility for market exclusivity.