In what scientists are calling a "monumental achievement," an experimental medication called ZMapp, given on a compassionate basis to a handful of Ebola victims in the current outbreak, cured 100% of monkeys treated in a Canadian study, researchers announced Friday.
ZMapp, made by Mapp Biopharmaceuticals of San Diego, is in the early stage of development and has never been formally tested in humans. In a study published Friday in the journal Nature, however, the drug allowed all 18 rhesus macaques infected with a lethal dose of Ebola to recover. The drug worked even when given five days after infection. The monkeys received three doses of ZMapp, administered three days apart, according to the study, which was conducted by the Public Health Agency of Canada.
The three monkeys that did not receive ZMapp died within eight days of infection.
In monkeys given ZMapp, however, the drug reversed severe symptoms, including severe bleeding, rashes and elevated liver enzymes, a sign of liver failure. Three weeks after infection, tests showed the surviving animals had no detectable Ebola virus in their blood.
"It's fantastic news," says study co-author Gary Kobinger of the Public Health Agency of Canada. "This strongly supports" the hope that ZMapp will work in humans, he says.
The results are "a monumental achievement," says Ebola researcher Thomas Geisbert of the University of Texas Medical Branch at Galveston, who was not involved in the current study but who wrote an accompanying editorial.
Doctors used a different strain of Ebola virus in their study than the one that's currently circulating in West Africa. However, they tested ZMapp in test tubes against the current strain and found that it blocked infection.
Although ZMapp hasn't been tested for safety in humans, its manufacturer shared a handful of doses with Ebola victims as a last-ditch effort to save their lives. Four of those patients — including two Americans and two Liberian health workers — survived after taking the drug. A fifth aid worker, who is now being treated in London, also has begun treatment with ZMapp. A Spanish priest and Liberian doctor given ZMapp died.
Mapp Biopharmaceuticals has said that there are no more doses of ZMapp left. The drug, which includes three man-made antibodies to Ebola, takes months to manufacture. The antibodies are intended to allow the patients' immune system to respond to Ebola and fight off the infection.
Given the limited experience with ZMapp in humans, it's not yet possible to know how ZMapp works in humans, Geisbert says.
That's because ZMapp has been given to only a handful of patients, with no control group for comparison, he says.
The Americans' cases are also unique. One of the American doctors who received ZMapp, Kent Brantly, also received a blood transfusion from a teenager who survived Ebola. So it's possible that the transfusion, not ZMapp, should get credit for saving him, Geisbert says. Receiving intensive care at Emory University Hospital in Atlanta — one of the best hospitals in the world — also could have helped the Americans survive.
Geisbert notes that about half of Ebola patients survive without taking ZMapp.
It's possible that the two Ebola patients who died after taking ZMapp got the drug too late, Geisbert says. There is a "point of no return," he says, after which time nothing can save someone with Ebola, which causes tiny leaks in blood vessels, leading to massive internal and external bleeding, as well as organ failure. The immune system also can overreact in the late stages of Ebola, causing more harm than good.
Three of the five species of Ebola virus are lethal to humans, Geisbert notes. A treatment that works against one species — or different strains of the same species — may not necessarily work against others.
Ebola has infected more than 3,000 people in Guinea, Sierra Leone, Liberia, Nigeria and Senegal, killing half of them, according to the World Health Organization. Senegal reported its first case of Ebola on Friday.
In a worrying development, researchers reported Thursday in Science that the Zaire strain of Ebola virus — the type now circulating in West Africa — appears to have mutated from its original form. The virus appears to be changing as it moves across Africa. Kobinger says he doesn't know how those mutations will affect the efficacy of ZMapp.
Doctors at the National Institutes of Health plan to launch the first human trial of an Ebola vaccine next week at the institute's campus in Bethesda, Md., using healthy volunteers. The early study, using just 20 volunteers, will assess the experimental vaccine's safety and ability to activate the immune system to recognize the Ebola virus.
Additional vaccine studies will be conducted in Bethesda, the United Kingdom and West Africa throughout the fall, NIH officials said Thursday. Early results from the first NIH trial are expected before the end of the year.
Five experimental vaccines under development have been shown to completely protect monkeys against Ebola, Geisbert says. But only one of those vaccines is effective in a single injection — as opposed to multiple shots — an important practical advantage when trying to vaccinate hundreds or thousands of people in developing nations.
Getting a usable treatment or vaccine could take many more months, however, officials caution. The best way to control the current outbreak is with traditional measures: diagnosing patients, isolating them, tracing their contacts and testing them, and extending the process out in circles, until all exposed patients have been isolated.