Experimental drugs poised for use in Ebola outbreak
Practical and ethical questions
Whether that will include deploying experimental drugs in addition to the vaccine is now under discussion. The WHO is consulting experts to consider the evidence for such treatments, and the medical humanitarian organization Médecins Sans Frontières (MSF) is talking to DRC officials about the possibility of using experimental Ebola medicines, says Annick Antierens, who coordinates Ebola clinical trials for MSF.
Although the rVSV-ZEBOV vaccine could help to prevent people from becoming infected, Antierens says, experimental treatments might still be needed because officials lack a thorough understanding of where Ebola first emerged during this outbreak or how it is spreading. So there are likely to be very many people who have already been infected.
“It we’re lucky and the disease doesn’t spread, the outbreak will be quickly resolved and we will have to use few experimental products,” Antierens says. “But if we’re unlucky we’ll need to use them.”
Administering experimental vaccines and drugs in an outbreak raises ethical and logistical complexities, such as delivering them to remote settings by aeroplane or motorbike and designing humane and rigorous clinical trials. The 2014–16 Ebola outbreak saw intense controversy over whether potential drugs and vaccines should be tested in randomized controlled trials, in which patients are assigned by chance to receive either the experimental treatment or standard care. MSF and officials at the WHO argued that withholding experimental medicines from patients who had few other options would be unethical.
The treatments MSF is now considering include the antibody treatment ZMapp, and two antiviral drugs, favipiravir and GS-5734, which were given to varying numbers of patients in the 2014–16 epidemic.
Zmapp, made by Mapp Biopharmaceutical in San Diego, California, was tested in a trial involving 72 patients; 22% of the 36 people who received the drug died, compared with 37% of the 35 who did not receive ZMapp. But the Ebola outbreak ended before the study was able to enrol the 200 people needed to obtain a statistically significant result.
ZMapp is also impractical for use in remote settings, such as parts of Bikoro and Iboko, the two health zones in Équateur province that have seen the most Ebola cases in this outbreak so far. There is an extremely limited supply of the drug, several doses must be administered by intravenous infusion under constant supervision, each infusion takes many hours, and the drug must be refrigerated.
Sparse data
Favipiravir, an antiviral drug made by the Japanese company Toyama Chemical, was given to 126 patients in the West African outbreak, and a few dozen patients in other trials. GS-5734 was given to three people, including an infant and a Scottish nurse who developed meningitis months after apparently recovering from an acute Ebola infection. Both the nurse and the infant survived; the infant was the first documented case of a baby surviving Ebola.
Favipiravir and GS-5734 would be easier than ZMapp to administer to patients during the outbreak, as neither needs to be refrigerated. But the drugs have not been proved to improve the chance that people will survive an Ebola infection, because the favipiravir trial was not designed to test efficacy, and GS-5734 has been tested in so few patients.
The Congolese Ministry of Health and a national ethics review board would need to greenlight trials of these treatments. Observers say that the trials, if approved, must proceed more equitably than they did in the 2014–16 outbreak, when experimental treatments were given first to international doctors and aid workers.
“We were pretty tone deaf. The interventions were used first and primarily on Westerners, including medevacing them out of the country and treating them,” says Lawrence Gostin, director of the WHO Collaborating Center on Public Health Law and Human Rights at Georgetown University in Washington DC. “We need to do that completely differently this time.”
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