Exploring the Role of Antiviral Drugs in the Eradication of Polio Workshop Report (2006) / Chapter Skim
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4 Development of Antiviral Drugs for Polio Virus
4 Development of Antiviral Drugs for Polio Virus
Pages 35-46
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From page 35... ...
The goal of this chapter is to discuss the steps that a potential antiviral drug will have to pass through to be successful. The first step is to identify what the drug must do and how it will be used, to write a "package insert," as it were, for the drug before it even exists.
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From page 36... ...
If ring prophylaxis with a medication and vaccine is expected, the number of people requiring treatment would be exceedingly large and require large quantities of medication. Successful development of an antiviral drug to prevent poliovirus transmission will require simultaneous attention to two challenges: active agents must be identified and optimized, and how the agent will be used must be carefully defined, because this will determine how it will be tested, regulated, and administered.
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From page 37... ...
has identified a member of the capsid-binding inhibitor class, V-037, that has significant in vitro activity against human poliovirus type 1 (Collett 2005)
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From page 38... ...
However, while protein binding is a fundamental concern in drug development, its application to the development of antiviral drugs is not well established. In vitro studies are performed using human blood, but their translation to probability of success in the clinic has not been established.
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From page 39... ...
Both vaccine-derived and wild-type polioviruses should be included. Initial assays can use whole virus replication with a plaque-reduction format.
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From page 40... ...
Once lead molecules for potential poliovirus antiviral drugs have been identified, a medicinal chemistry program will need to be initiated to refine the molecules to optimize inhibitory properties. Contract medicinal chemistry companies (of which there are many with substantial expertise in the United States and abroad)
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From page 41... ...
CLINICAL DEVELOPMENT At the outset of polio antiviral drug development, the clinical development pathway should be defined. A key component in the development of potential therapeutic molecules will be a detailed consideration of whether vaccine-challenge studies or transmission studies can be performed.
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From page 42... ...
. The clinical trial development of molecules to inhibit human poliovirus replication should be considered in a traditional format.
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From page 43... ...
THE IMPORTANCE OF DEVELOPING MORE THAN ONE ANTIVIRAL DRUG The identification, optimization, and testing of drugs for the treatment of poliovirus infections is a complex process that is inherently unpredictable. Any potential lead could be proved unsuitable at any stage of the process.
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From page 44... ...
TIMELINES AND COSTS One issue that deserves careful consideration is whether a polio antiviral drug can be developed in time to contribute to the global eradication program. If current plans are followed, OPV will continue to be used for up to 6 years after the last wild poliovirus infection is detected.
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From page 45... ...
In agreement with this number, one published report estimates the average out-of-pocket clinical period costs for investigational compounds to be $60.6 million in 2000 dollars (DiMasi et al.
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From page 46... ...
They could include the Bill and Melinda Gates Foundation or a new foundation dedicated specifically to the development of a polio antiviral drug as a component of the global polio eradication program. The Rotary Club does not have such a foundation in place, but it has invested over $650 million in the eradication of polio and might regard the development of an antiviral as a good backup to ensure the eventual success of its investment.
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