both help to keep the cost low and will be likely to reduce safety risks. EC50 is defined as the drug concentration that inhibits 50% of virus replication; EC90 is the dose that provokes a response that is 90% of the maximum. The EC50 and EC90 should be in the low nanogram range. In addition to showing substantial antiviral activity, a molecule suitable for development must be amenable to large-scale, cost-effective synthesis. Difficulties in synthesis will be directly reflected in higher costs.

Chapter 2 further suggested that the most likely application of a polio antiviral drug would be in combination with inactivated poliovirus vaccine. 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.

POTENTIAL HURDLES TO ADDRESS AT THE OUTSET

At the outset of a program designed to develop drugs to treat poliovirus infections, potential hurdles should be identified. Development of medications for therapy of poliovirus infections historically has not attracted support from the pharmaceutical industry. The committee does not envision industry support of development costs, so a fundamental question that needs to be resolved is: Who will fund the development of these medications? As clinical trials are envisioned, a parallel question will be: Who will hold the investigational new drug application? Those two questions should be addressed at the outset of any initiative. A credible clinical development plan that ensures the project could proceed beyond preclinical proof of concept will be critical to attract support for such a program. Because it is envisioned that these drugs will be used globally, it would be helpful to establish an international collaboration of responsible individuals, including regulatory authorities, at the outset of the program.



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