The United States Food and Drug Administration (FDA) last week issued final guidance for developing smallpox treatment studies, providing clarity to drug manufacturers.
“Despite recent advances in developing an effective treatment for smallpox, drug developers still face challenges in bringing forward these medical countermeasures, which are critical should smallpox ever be used as a biological weapon,” Anna Abram, FDA Deputy Commissioner for Policy, Legislation and International Affairs, said. “The agency’s work to advance safe and effective medical countermeasures is a high priority, and today’s final guidance on the development of drugs to treat or prevent smallpox builds upon currently available guidance, further advancing the agency’s long-standing commitment to the development of robust medical countermeasure preparedness efforts.”
The new guidance is called Smallpox (Variola Virus) Infection: Developing Drugs for Treatment or Prevention.
Smallpox remains one of the great viral history lessons. At its peak in the 20th century, it killed tens of millions annually. A concerted global effort was put toward its eradication, which only succeeded in 1980, according to the World Health Organization (WHO). Dr. Robert Kadlec, Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), has dubbed smallpox as one of the deadliest diseases known to mankind.
Today, two known labs are approved to have the smallpox virus for research: the Center for Disease Control and Prevention (CDC) and the Russian State Centre for Research on Virology and Biotechnology. Concerns remain among experts that smallpox could be used as a biological weapon – a particularly dangerous threat, given that routine smallpox vaccinations in the United States have been discontinued since the 1970s, leaving most of the population without immunity to the deadly disease.
It makes for a complex situation for drug developers, who have sought a regulatory pathway for smallpox drug development.
The latest guidance provides exactly that, building off a draft guidance issued last year. It establishes the recommended abilities of animals in key studies to be able to invoke appropriate immune responses, since ethical issues preclude use of smallpox studies on humans. In that regard, they ask that sponsors consider differences in disease development time frames between humans and animals when designing studies, and perform a direct serologic analysis for larger animals or indirect analyses for rodents for monitoring purposes.
Studies of any nature involving smallpox must be conducted in collaboration with the CDC, with approval from the WHO.
“The FDA plays a pivotal role preparing our nation to be able to protect the American people from biological threats, including by providing guidance and support for the development of medical countermeasures that can be used safely, effectively and reliably during public health emergencies,” Abram said. “We work with government partners as well as non-government organizations, universities and research centers, and industry to further the development of medical countermeasures as part of our vital public health mission.”
The U.S. government has vaccines, treatments and other materials stockpiled in the event of a smallpox incident, but the ongoing worry of an outbreak leaves options for new treatment development open, as in the case of this guidance.
Earlier this year, a report entitled, A World at Risk: Annual report on global preparedness for health emergencies, from the Global Preparedness Monitoring Board warned of the real possibility of a pandemic threat. Such an event could kill up to 80 million people, the report warned, evoking reminders of what smallpox once regularly achieved.
“A global pandemic on that scale would be catastrophic, creating widespread havoc, instability and insecurity. The world is not prepared,” report authors said.