March 4, 2015

NIAID Announces Joint U.S.-Liberia Clinical Trial for Ebola Virus Antiviral Drug

The Ebola virus disease crisis continues in western Africa. To date, in the hardest-hit countries of Liberia, Guinea and Sierra Leone, at least 23,913 cases are reported by the World Health Organization (WHO), with 9,714 deaths. At the height of the Ebola outbreaks on several continents last fall, the experimental biotech drug, ZMapp, made by Mapp Biopharmaceutical of San Diego, and comprised of several humanized monoclonal antibodies, was given to several U.S. health care workers who had contracted the virus while working in western Africa, with positive results. Although no drug had received formal approval for treating Ebola virus disease, WHO assembled an expert panel to consider the ethical implications of using non-approved, but potentially promising drugs (including ZMapp) during the expanding Ebola crisis; a summary of their consultation stated: 
In the particular circumstances of this outbreak, and provided certain conditions are met, the panel reached consensus that it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention. 
Now, the first formal clinical trial for ZMapp has been announced by the National Institute of Allergy and Infectious Disease (NIAID)
In partnership with the Liberian government, the National Institute of Allergy and Infectious Diseases (NIAID) today launched a clinical trial to obtain safety and efficacy data on the investigational drug ZMapp as a treatment for Ebola virus disease. The study, which will be conducted in Liberia and the United States, is a randomized controlled trial enrolling adults and children with known Ebola virus infection.

“Although ZMapp has been used to treat several Ebola-infected patients in recent months, we cannot determine if the drug actually benefitted those patients because it was not administered within the context of a clinical trial,” said Anthony S. Fauci, M.D., director of the NIAID, at the National Institutes of Health (NIH). “This clinical trial will help us determine if ZMapp and other treatments are safe and effective for use in the current devastating outbreak in West Africa as well as in future outbreaks. 

ZMapp, developed by Mapp Biopharmaceutical Inc., based in San Diego, is composed of three different proteins called monoclonal antibodies. ZMapp is designed to prevent the progression of Ebola virus disease within the body by targeting the main surface protein of the Ebola virus. The antibodies comprising ZMapp are produced in tobacco plants specially bioengineered to produce large quantities of these proteins. Studies in nonhuman primates demonstrated that ZMapp has strong antiviral activity and rescued the animals from death as late as five days after infection with Zaire ebola virus. The drug has not yet been tested in human clinical trials, but was administered under emergency use authorization to nine infected patients in Africa, the United States, and Western Europe. 
The current picture for containing Ebola virus is mixed; while western Africa is still a focus of public health and relief efforts, there are warnings regarding the possibility that other countries with poor public health infrastructure could be susceptible to future outbreaks. Furthermore, there is still no vaccine available, although some promising candidates are in development. From the U.S. perspective, the American troops committed to public health assistance in western Africa are being withdrawn. The Ebola "czar" has now finished his term, and has called for improving the WHO response capacity, decreasing reliance on overburdened NGOs and establishing a formal international public health responder force ready to be deployed in similar crises. The Ebola crisis illustrates a paradox of modern public health management: specific therapeutic options may originate in cutting-edge biotechnology, but the overall containment of any infectious disease crisis is equally dependent on the availability of basic, old-fashioned public health infrastructure.

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