Background: Enteroviral sepsis can cause severe morbidity and mortality among neonates. There is no effective treatment. Pocapavir (V-073) is an investigational enterovirus (EV) capsid inhibitor being developed for poliovirus indications. In-vitro studies show activity against other EVs including coxsackieviruses and echoviruses. Monochorionic diamoniotic twins born at 27 weeks gestation acquired nosocomial EV infection and were treated with pocapavir. At 2 months old, Twin B developed respiratory distress and apnea, followed quickly by liver, cardiac and hypoxemic respiratory failure, metabolic acidosis, profound anemia and thrombocytopenia. Twin B's serum EV PCR was positive day of illness (DOIB) 2 and IVIG treatment was given. Twin A developed abdominal distension, fever, and apnea 1 day after Twin B became ill and also received IVIG. Twin A developed moderate anemia and thrombocytopenia, and mildly elevated AST/ALT, and on DOIA 2 serum EV PCR was positive. Cerebral spinal fluid from twin A as well as throat and rectal swabs from both twins were EV positive by PCR.
Methods: Emergency investigational new drug approval for pocapavir treatment was obtained from the FDA and consent obtained from the parents. 25mg/kg/day of pocapavir was given via nasogastric tube. Virus culture and pocapavir susceptibility in serum samples were measured in HeLa cells. Drug plasma levels were determined by LC-MS/MS.
Results: CDC molecular typing identified coxsackievirus B3 from both twins. Virus from pre-dose serum samples had median effective concentration (EC50) values for pocapavir of 39-60 ng/mL. Plasma drug levels at 6-8 hours post–dose were 132-312 ng/mL. Twin B received pocapavir DOIB 4-7, but progressive liver failure and coagulopathy led to severe intracranial bleeding and withdrawal of support on DOIB 7. Twin A received pocapavir DOIA 3-16 and recovered without sequelae. After 5 days dosing, Twin A had no detectable EV on cell culture from serum sample. No drug-related adverse events were noted.
Conclusion: Pocapavir is a potential treatment for neonatal EV sepsis. For these preterm twins, one with severe fulminant disease died after 4 days treatment while the other twin with less advanced disease tolerated therapy well and had reduction in EV titers coincident with clinical improvement.
S. Oberste, None
J. Hincks, ViroDefense, Inc: Board Member , Employee and Shareholder , Salary
M. Collett, ViroDefense Inc: Board Member , Employee and Shareholder , Salary
C. Wright, None
E. Asturias, None