A Reynolds American plant in Owensboro, Ky., makes ZMapp inside the leaves of tobacco plants, but production is very limited.
Inside special isolation units at an Atlanta hospital on Wednesday, Kent Brantly and Nancy Writebol, the two Americans infected with Ebola in West Africa, appeared to be responding to an experimental medicine devised by an obscure biotechnology company with ties to the Defense Department.
In West Africa, the estimated death toll from the outbreak kept rising, to 932, by the latest official count.
How and why Dr. Brantly and Ms. Writebol received the drug, ZMapp, is one of the many mysteries surrounding what has been called a “secret serum,” including the big one: Does it really work? The Americans are the only two patients who have been treated with the medicine, out of perhaps thousands who might have benefited so far, raising old questions about who does — and does not — have access to medications, including experimental drugs.
In West Africa, the estimated death toll from the outbreak kept rising, to 932, by the latest official count.
How and why Dr. Brantly and Ms. Writebol received the drug, ZMapp, is one of the many mysteries surrounding what has been called a “secret serum,” including the big one: Does it really work? The Americans are the only two patients who have been treated with the medicine, out of perhaps thousands who might have benefited so far, raising old questions about who does — and does not — have access to medications, including experimental drugs.
“It’s absolutely overwhelming,” Larry Zeitlin, the president of Mapp, said in an interview Wednesday. “We are discussing with the F.D.A. the right path to make the drug available to people as quickly and safely as possible,” he added, referring to the Food and Drug Administration.
There were signs that efforts to increase production were beginning. Caliber Biotherapeutics, a Texas company established with funding from the Defense Department to respond to biological threats, has received inquiries from the government about whether it could help manufacture ZMapp, said R. Barry Holtz, the company’s chief science and technology officer.
The World Health Organization said it would convene a panel of medical ethicists early next week to explore the use of the experimental treatment in the outbreak in West Africa. Currently, neither ZMapp nor any other medicine or vaccine is approved for treatment of the virus, but there are several experimental options under development.
How quickly the drug could be made on a larger scale will depend to some extent on the tobacco company Reynolds American. It owns the facility in Owensboro, Ky., where the drug is made inside the leaves of tobacco plants. David Howard, a spokesman for Reynolds, said it would take several months to scale up.
Mapp was started in 2003 by Dr. Zeitlin and Kevin J. Whaley. They have worked together for many years, starting at Johns Hopkins University, on research that uses crops to produce immune system proteins to treat diseases in people.
Dr. Whaley, the chief executive of Mapp, and Dr. Zeitlin have not spoken much publicly since the news of the treatment broke on Monday, saying they are too busy and want to avoid the limelight. The privately held company has only nine people and has been financed solely by government grants and contracts, they said.
“We definitely would like to ramp up to have an impact on the Ebola epidemic,” Dr. Whaley said. But he added, “We’re not decision makers on many of these issues. There are regulatory and legal issues that have to be addressed.”
The drug had never before been tried in people, though it and some predecessor drugs had been tested in monkeys, showing some effectiveness. Mapp was only now gearing up to start the larger animal toxicity studies typically needed before testing it in humans, with an eye to doing the first human safety studies in healthy volunteers next year. For that reason there were very few doses available when the Ebola outbreak started.
Now the company is trying to move faster and it is likely the drug will be tested in patients rather than healthy volunteers.
ZMapp uses an approach called passive immunotherapy. Instead of having a vaccine stimulate the immune system to make antibodies that attack the virus, passive immunotherapy simply supplies the antibodies to the patients. For some infectious diseases, these antibodies are extracted from the blood of patients who have survived the infection and presumably have effective antibodies.
ZMapp instead consists of antibodies that are made by exposing mice to a key Ebola protein and harvesting their antibodies. Those antibodies are then genetically modified to make them more like human antibodies and therefore less likely to provoke an immune reaction if injected into people.
Nancy Writebol Credit SIM International, via European Pressphoto Agency
The gene for each antibody is then introduced into the leaves of tobacco plants using a system developed by Icon Genetics, a German company. The leaves then produce the antibody.
In one study published last year, three out of seven monkeys treated with antibodies developed by Mapp survived being infected with Ebola, even though treatment did not start until four days after the infection. Both animals in the control group died. The treatment worked even better in another study when begun earlier after exposure to the virus.
It turns out another tiny company, Defyrus, based in Toronto, was independently developing a similar treatment with the Public Health Agency of Canada.
The companies agreed to combine the best of their antibodies into a single cocktail called ZMapp, which is what the two American aid workers received. The data for ZMapp in monkeys has not been published but is said to be substantially better than for the predecessor drugs.
Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said it was “too early to make any conclusions about how effective this intervention is,” since it was tested in only two people.
A man washes his hands as part of a campaign to prevent the spread of the Ebola virus in Monrovia, Liberia.Expert Panel to Consult on EbolaAUG. 6, 2014
Gwendolyn Davis, 63, a retired schoolteacher, folded her laundry in the Bronx.Ebola Outbreak Hits Home for New York’s West African ImmigrantsAUG. 5, 2014
Health workers informed residents about the Ebola virus on Monday in Freetown, Sierra Leone.Sierra Leone Deploys Troops in Ebola CrisisAUG. 5, 2014
Times Topic: The Ebola Outbreak in West Africa
But the San Diego-based Mapp Biopharmaceutical, the primary developer of the drug, was consumed Wednesday with how to manufacture more of it with an eye to providing the drug to more patients, probably in the form of clinical trials.
