The Poliovirus Antivirals Initiative
In February 2006, the National Research Council (NRC) of the (US) National Academies issued the report: Exploring the role of antiviral drugs in the eradication of polio. The report concluded that “…it would be prudent to develop at least one, but preferably two, polio antiviral drugs as a supplement…for the control of poliomyelitis outbreaks in the post eradication era.” The report further recommended forming a drug development team to guide the effort.
In response to the NRC recommendations, The Task Force for Child Survival and Development (TF) in Atlanta, USA, established the Poliovirus Antivirals Initiative (PAI), in partnership with the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institute for Allergy and Infectious Disease (NIAID). A multidisciplinary Steering Team consisting of five independent experts coordinates the efforts of drug sponsors. Currently there are two drug sponsors: ViroDefense, Inc. (capsid inhibitor) and Pfizer, Inc. (protease inhibitor). Both drug candidates are in early stages of development.
There are three situations anticipated for polio antiviral drug use:
- for immunodeficient individuals chronically shedding poliovirus
- for persons exposed to poliovirus (e.g. through unintentional laboratory exposure)
- (likely in conjunction with inactivated polio vaccine – IPV) for communities exposed to a circulating vaccine-derived poliovirus (cVDPV) in the post-eradication era.
The immediate PAI goal is to determine if a candidate compound is safe and has the capacity to prevent, reduce, or stop virus shedding when administered to adult volunteers before or after OPV challenge. If successful, these “proof-of-concept” results should permit the opportunity to apply for a compassionate use investigational new drug (IND) for treatment of persons chronically shedding poliovirus (situation 1) and individuals exposed in a laboratory incident (situation 2). Proof-of-concept results will also permit assessment of the drug’s practical utility for community outbreaks (situation 3) and allow “go-no-go” decisions for further development.