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Web Date: August 29, 2014

Experimental Drug Reverses Ebola In Infected Monkeys

ZMapp’s efficacy in macaques drives researchers to call for rapid human safety testing of blend of monoclonal antibodies
Department: Science & Technology
Keywords: Ebola, ZMapp, monoclonal antibodies, West Africa Ebola outbreak

An experimental group of 18 seriously ill monkeys infected with the Ebola virus has recovered after treatment with a cocktail of monoclonal antibodies, according to a paper in Nature (2014, DOI: 10.1038/nature13777), scientists announced on Aug. 29.

The results are prompting researchers to call for hastening of efforts to determine the human safety of the therapy, known as ZMapp, in light of the current severe Ebola outbreak in West Africa.

According to a World Health Organization estimate, the outbreak, which is the worst in history, may eventually lead to 20,000 infections and cost $490 million before it’s contained. The Ebola strain in this outbreak has a fatality rate of over 50%, but some strains have fatality rates of up to 90%.

A team including Gary P.Kobinger and Xiangguo Qiu of the University of Manitoba, Mapp Biopharmaceuticals in San Diego, and others has been studying various combinations of monoclonal antibodies that have shown promise in treating monkeys recently infected with Ebola.

In the current study, they optimized the cocktail, which they call ZMapp, to contain three antibodies. They then infected 18 rhesus macaques with lethal doses of the Ebola virus. The monkeys were each given three doses of the cocktail, spaced apart by three days. All recovered, even those who were first treated after they had been infected for five days. Many were experiencing the dramatic symptoms of Ebola, such as high fever and hemorrhaging.

“The level of improvement was beyond my expectations,” Kobinger said at an Aug. 29 press briefing. “We could rescue some with advanced disease just a few days, even a few hours, from the end.”

Even before they were published, these promising results prompted the recent compassionate ZMapp treatment of seven Ebola victims, including two Americans who were transported to the U.S. after being infected in Africa. Both Americans survived. However, a Spanish priest and a Liberian doctor died. Others are still in treatment.

Kobinger said these seven cases were not treated in the context of a clinical trial and that data about doses and timing need to be studied before any conclusions can be drawn about the treatment’s effectiveness in humans.

Mapp Biopharmaceuticals will spearhead Phase I clinical safety trials in humans in early 2015, Kobinger said. Kobinger and Qiu said at the conference that they expected the human dosing protocol to be similar to that given to the monkeys: three doses each of 50 mg/kg. “One dose is probably not enough,” Qiu said.

In a perspective accompanying the Nature paper, Thomas W. Geisbert of the University of Texas Medical Branch called the work “a monumental achievement.”

All of the researchers noted that the therapy is difficult to produce in large quantities. Kobinger said that for now, labs would be able to produce only 20 to 40 doses per month.

Although the monkeys in the current study were infected with a lab reference Ebola strain, the Kobinger team also showed that ZMapp inhibited growth of the Ebola strain behind the current West African outbreak.

 
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