5
Implementation and Recommendations

THE COMMITTEE RECOGNIZES THAT IDENTIFYING the resources to develop an antiviral drug against poliovirus will be challenging. Public health needs are vast and the polio eradication effort is drawing to an end with the anticipated cessation of oral poliovirus (OPV) global campaigns. The public health burden of paralytic polio that has been lifted as a result of the eradication effort has been enormous. The Global Polio Eradication Initiative estimates that over $4.6 billion has been spent on the polio eradication effort to date (Global Polio Eradication Initiative 2006). The committee thinks that it is important to ensure that past investment in the eradication effort be protected. There are two major threats to maintaining a polio-free world. First, the eradication effort involved a live vaccine that carries the risk of initiating new chains of transmission, especially in the early post-OPV years. Second, the risk of accidental or intentional release of poliovirus cannot be entirely eliminated and the consequences of such a release will grow more and more serious after routine immunization ceases.

Therefore, the committee concludes that if current plans to cease OPV administration go forward, it is important to begin development of at least one, but preferably two, polio antiviral drugs as a supplement to the tools currently available for the control of poliomyelitis outbreaks.

The successful development of antiviral drugs against poliovirus will require coordinated and sustained attention to a number of challenges: defining how the compound will be used, choosing the best targets, investing in the most promising lead compounds, determining the most



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Exploring the Role of Antiviral Drugs in the Eradication of Polio: Workshop Report 5 Implementation and Recommendations THE COMMITTEE RECOGNIZES THAT IDENTIFYING the resources to develop an antiviral drug against poliovirus will be challenging. Public health needs are vast and the polio eradication effort is drawing to an end with the anticipated cessation of oral poliovirus (OPV) global campaigns. The public health burden of paralytic polio that has been lifted as a result of the eradication effort has been enormous. The Global Polio Eradication Initiative estimates that over $4.6 billion has been spent on the polio eradication effort to date (Global Polio Eradication Initiative 2006). The committee thinks that it is important to ensure that past investment in the eradication effort be protected. There are two major threats to maintaining a polio-free world. First, the eradication effort involved a live vaccine that carries the risk of initiating new chains of transmission, especially in the early post-OPV years. Second, the risk of accidental or intentional release of poliovirus cannot be entirely eliminated and the consequences of such a release will grow more and more serious after routine immunization ceases. Therefore, the committee concludes that if current plans to cease OPV administration go forward, it is important to begin development of at least one, but preferably two, polio antiviral drugs as a supplement to the tools currently available for the control of poliomyelitis outbreaks. The successful development of antiviral drugs against poliovirus will require coordinated and sustained attention to a number of challenges: defining how the compound will be used, choosing the best targets, investing in the most promising lead compounds, determining the most

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Exploring the Role of Antiviral Drugs in the Eradication of Polio: Workshop Report appropriate approach to proving efficacy and safety and—most importantly—raising awareness of the importance of the task and mobilizing the necessary funds. Therefore, the committee recommends that a multidisciplinary steering team be assembled to guide the effort. RECOMMENDATIONS 1. Public Health Considerations The committee recommends that: The development of one or more polio antiviral drugs should be included as a goal of the global polio eradication effort. Under the assumption that administration of OPV will eventually be halted, the availability of an effective polio antiviral will be extremely useful for outbreak control in the context of declining levels of population immunity. The primary use of the antiviral/s should be to assist, possibly with IPV, in control of a cVDPV outbreak in the post-OPV era by preventing virus spread through prophylaxis of susceptible contacts and reduced virus shedding of infected persons. Treatment of patients chronically infected with poliovirus would be a secondary use of the antiviral drugs, but careful attention should be paid to the risk that resistant strains could emerge during long-term use. Careful consideration should be given to plans including criteria for employment of the drug, a distribution strategy, and innovative ways of enhancing compliance. Deployment of the antiviral or antiviral drugs should be under the control of public health authorities. 2. Biological Considerations The committee recommends that: Capsid-binding molecules and 3C protease inhibitors initially be given priority for consideration: the availability of promising lead compounds, the critical replication functions interrupted by these classes of compounds and the likelihood that these compounds may

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Exploring the Role of Antiviral Drugs in the Eradication of Polio: Workshop Report thwart the emergence of resistance combine to make them the most attractive candidates for initial consideration. Additional targets including 2Apro, 3Dpol, 2C, 3A and RNA structures also be explored, so that information about their activity will be available if screening programs identify compounds with antipolio activity. Developments in novel therapeutic approaches like siRNA, morpholinos and passive antibodies be carefully monitored; significant technological advances in these approaches could unexpectedly make one of them the most feasible and cost-effective approach to developing a polio antiviral. Continued basic research into poliovirus should be encouraged. Improved understanding of the sites of replication and the development of appropriate animal models of infection, pathogenesis and shedding will make the development of a polio antiviral much more likely to succeed. 3. Developmental Considerations The committee recommends that: Compounds acting against at least two targets be developed in parallel. Funding be pursued to formulate a development plan, including considering carefully the most promising compounds for development, generating realistic budget estimates, and mapping out the clinical trial and regulatory approval processes. A drug development team be formed to guide the effort; the team should include public health experts (including representatives from countries where the antiviral might be tested and/or deployed), molecular biologists with expertise in poliovirus biology, clinical drug developers and industry representatives.

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