Our Work

The Polio Eradication Initiative (PAI) is the cornerstone of the Task Force's Global Polio Eradication work. The PAI is a public/private partnership formed in 2008 by The Task Force in response to the 2006 report of the National Research Council (NRC) of the (US) National Academies. The NRC report on “Exploring the role of antiviral drugs in the eradication of polio” (2006, National Academies Press, Washington, D.C.) concluded that “… it would be prudent to develop at least one, but preferably two, polio antiviral drugs as a supplement to the tools currently available for the control of poliomyelitis outbreaks in the post-eradication era." Recognizing the absence of a commercial incentive for developing an antiviral, the NRC recommended formation of a “public/private partnership” to “provide the most efficient and least expensive means to develop antiviral drugs against polioviruses."

Work of the PAI
The aim of the PAI is to facilitate the rapid, cost-efficient development of at least two safe and effective poliovirus antiviral drugs with differing modes of action or distinct drug resistance profiles to provide a hedge against possible treatment-emergent drug resistance. Proof of concept oral polio vacccine (OPV) challenge studies in healthy immunocompetent adults are the safest and most efficient path to assessing the effectiveness of drug candidates in the target patient population. OPV challenge studies in healthy adults also broadly inform post exposure prophylaxis options for persons in special situations as a result of intentional or unintentional laboratory release. These data will also provide guidance on potential studies of optimum dosing in pre-exposure situations, such as community members following an outbreak of cVDPV.

The PAI strategy was driven by NRC recommendations, anticipated limited funds for drug development and the programmatic desire for early drug availability. The work of the PAI is directed by a Steering Team comprised of some of the leading organizations and researchers in the field of polio antivirals. The Steering Team is responsible for guiding the work of the PAI, including review of proposed work plans, timelines, and estimated costs of drug development as well as options and issues pertaining to field implementation.

Consistent with the NRC recommendations to “give initial priority to compounds investigated for related viruses”, the PAI strategy has been to identify developmentally advanced compounds with possible poliovirus activity, confirm the breadth of activity against a standard in vitro poliovirus panel, and direct development of promising compounds toward poliovirus indications. Of 11 top candidates screened, three met the established in vitro criteria for efficacy and toxicity. Two are currently are under development: a capsid inhibitor V-073 (ViroDefense Inc) and a protease inhibitor AG7404 (Pfizer Inc). The lead candidate V-073 has advanced to Phase 1 first-in-human studies. Early Phase 1 results with AG7404 have been previously published.

Next developmental steps include the clinical evaluation of the two lead drug candidates to first POC OPV challenge studies in healthy adults, followed by treatment of immunodeficient individuals who chronically excrete iVDPV. While current drug development follows the path to patient monotherapy, the stage will be set for future combination antiviral therapy by establishing the safety and pharmacokinetic parameters of the drug candidates when coadministrated.

Funding for the PAI
Since its inception, PAI has received financial support from the Centers for Disease Control and Prevention (CDC); the Global Polio Eradication Initiative, World Health Organization (WHO); and the Bill and Melinda Gates Foundation (BMGF). BMGF has provided the bulk of the funding through grants to Rotary International, WHO, and a direct grant to the Task Force as PAI secretariat. Extensive in-kind research and development support  has been provided by the CDC; the National Institute for Allergy and Infectious Diseases (NIAID), National Institutes for Health; Center for Biologics Evaluation and Research (CBER), Food and Drug Administration; and Pfizer Inc.