August 5, 2014

expert reaction to news reports on treatments for Ebola

News outlets have reported on experimental treatments for Ebola given to two American doctors who contracted the disease.

Prof Tom Solomon, Director of the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, and Director of the Institute of Infection and Global Health, University of Liverpool, said:

Q1. What new treatments are being tried for Ebola?

A1. “Although there are no proven antivirus treatments for Ebola, an experimental drug has been used in two American health care workers who became infected, with apparently encouraging results in one of them. The drug called ZMapp consists of humanized monoclonal antibodies against the virus, developed by San Diego Mapp Biopharmaceutical Inc, in collaboration with LeafBio, and Defyrus Inc. It uses some of the most sophisticated techniques for drug development that we have.”

Q2. How was the experimental drug developed?

A2. “The new treatment incorporates some neat scientific tricks which bring together human, mouse, and plant biology systems. Monoclonal antibodies are made by infecting a mouse with Ebola virus, and then isolating the immune cells (the clonal cells) which produce specific antibody proteins against the virus. Although they are effective at neutralizing the virus, these antibodies have to be modified, or “humanized,” so they are similar to human antibodies, and can thus work with the human immune system. These changes are made by altering the genes which produce the antibody proteins. The genes are injected into a tobacco plant, Nicotiana, which then produces large amounts of the antibody protein. The Zmapp treatment consists of three different monoclonal antibodies against Ebola virus proteins. So far it has proved effective when used to treat experimentally infected monkeys. Normally further drug development for humans would take years, with carefully controlled clinical trials. However, in emergency situations like this when the death rate from a disease is especially high, drugs can be used on a compassionate basis, without the full set of data to support their use.

“The first Ebola patient to receive ZMapp appeared to make a dramatic recovery within an hour, whereas in the second recipient there were no immediate effects. Such dramatic recoveries are unusual for any drug treatments, making some scientists cautious about how to interpret these findings. Full controlled clinical trials will be needed.”

Q3. What about use of serum?

A3. “The other way to get hold of antibodies against Ebola is simply to extract serum containing the antibodies from the blood of patients who have survived. Survivors of Ebola often have large amounts of antibody in their blood, and this can be extracted as serum, and then given to patients who are sick. Such serum has been used in Ebola outbreaks previously. For example 8 patients were treated with blood transfusions during the 1995 Ebola outbreak in the Democratic Republic of the Congo, seven of whom survived. During the current outbreak, serum from a child who survived Ebola appears to have been offered to the two Americans, a couple of days before they received the Zmapp drug.”

Q4. Will we ever have a proven drug treatment for Ebola?

A4. “Given that Ebola outbreaks have been occurring since 1976, and there have been major advances in drug development since then, it is disappointing that once again experimental drugs are being used on a compassionate basis only, rather than in the context of a clinical trial. This means that, at best, we will think that a drug works, but will not really have the evidence that proves it.  Pharmaceutical companies are unlikely to invest the massive resources into a drug which is only needed occasionally, and only in a few hundred people, most of whom live in the poorest parts of Africa. Investment is needed from international agencies such as the Bill and Melinda Gates Foundation, Wellcome Trust, and international aid agencies. In addition, for an unpredictable sporadic disease, with high mortality rates, we need a flexible approach to our clinical trials frame-work that short-cuts some of the normal regulatory hurdles. Rather than dragging through years of early stage clinical trials on healthy volunteers (which is the usual approach), and risks abandoning treatments which may have minor side effects in such volunteers, we need to be able to progress to phase III clinical trials on patients that are dying. Generic study protocols should receive ethical approval in advance of an outbreak, so that studies can start as soon as they are needed.”

Declared interests

None declared