The challenges of developing an antiviral agent for the treatment of smallpox using the animal efficacy rule

Abstract

Smallpox, eradicated in the late 1970s, is considered a serious worldwide threat because of its potential use as a biological weapon. Attempts to develop an antiviral drug for the prophylaxis and treatment of the disease are complicated by the need to demonstrate effective antiviral activity and propose human dosing paradigms based on data generated in animals infected with related orthopoxviruses. This perspective article reviews the difficulties associated with developing an antiviral agent using animal models and the ‘animal efficacy rule’: a FDA regulation designed for situations where human clinical trials are not an option.