Antiviral activity of pocapavir in a randomized, blinded, placebo-controlled human oral poliovirus vaccine challenge model

Abstract

Background.Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.Methods.In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined.Results.A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2–18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study.Conclusions.Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility.Clinical Trials Registration.EudraCT 2011-004804-38.

Emergency Services of Viral RNAs: Repair and Remodeling

“…However, populations of this very sensitive virus always contain tiny proportions (depending on the drug concentration tested) of guanidine-resistant (g r ) mutants (61), or even mutants whose growth requires the presence of this drug (62; also see below). The presence of drug-resistant and drug-dependent variants in largely sensitive populations has also been reported for other picornaviruses and other inhibitors (63)(64)(65)(66)(67)(68)(69)(70)(71). Different variants within heterogeneous viral populations may complement each other in performing some functions, as appears to be the case with poliovirus (10,14,22,32), although the converse situation, negative trans-dominance of debilitating mutations, has also been documented (72,73).…”

Meeting report: 32nd International Conference on Antiviral Research

“…Both are highly active against all three strains of vaccine virus, and show synergistic activity, with minimal toxicity. To date, only pocapavir has been tested for efficacy in human volunteers (Collett et al, 2017). The results suggest that combination therapy will be required to block the evolution of resistant virus.…”

Successful treatment of fulminant neonatal enteroviral myocarditis in monochorionic diamniotic twins with cardiopulmonary support, intravenous immunoglobulin and pocapavir

“…Both patients completed a course of 4 doses of 0.5 g/kg/dose IVIG and 18 oral doses of 25 mg/kg/dose (62 mg/dose) of pocapavir, an enterovirus capsid inhibitor, under Emergency Investigational New Drug approval from the Food and Drug Administration. Pocapavir dosing was determined based on a previous adult study5 and a compassionate use study in paediatric patients (ViroDefense) showing tolerability and predicated activity of plasma levels achieved at the given dose. Dosing duration was continued for 18 days until no further decreases were observed in enterovirus (EV) polymerase chain reaction (PCR) levels.…”