Thursday, August 15, 2019
On Monday morning, Director Anthony Fauci of the United States National Institute of Allergy and Infectious Diseases (NIAID), announced a trial of four possible Ebola drugs was stopped early because two of them had already shown considerable progress in treating the disease and saving the lives of those infected. Ebola virus disease (EVD) is a hemorrhagic fever with a high mortality rate and spreads via human-to-human contact.
The PALM trial, for the Swahili phrase pamoja tulinde maisha or “together save lives,” began last November and collected data from 499 patients from the towns of Beni, Butembo, Mangina, and Katwa in the Democratic Republic of the Congo, which has suffered an Ebola outbreak for roughly the past year.
Professor Jean-Jacques Muyembe, Director General of the DRC’s Institut National de Recherche Biomédicale that monitored the trial, said, “From now on, we will no longer say that Ebola is incurable[.]” He went on to say thousands of deaths could be prevented.
While one experimental vaccine appears able to reduce Ebola mortality, up until now, no drugs have been clearly demonstrated suitable for treating existing infection. One antibody cocktail, ZMapp, initially showed promise in the field, but formal studies indicated it had less benefit than sought in preventing death. In the PALM trial, ZMapp served as a control, meaning scientists used it as a baseline and compared the three other treatments to it.
The other three treatments were remdesivir, an antiviral drug; mAb114, a monoclonal antibody first isolated from human survivors of an outbreak in Kikwit in 1995, now produced by the Florida company Ridgeback Biotherapeutics; and REGN-EB3, a cocktail of three monoclonal antibodies from Ebola-infected laboratory mice whose immune systems had been altered to be similar to humans’.
The overall mortality rates were 49% for patients treated with ZMapp, 53% for remdesivir, 29% for REGN-EB3, and 34% for mAb114, but patients treatment early with low viral loads had a death rate of only 6% to 11% when treated with REGN-EB3 or mAb114.
Mike Ryan of the World Health Organization (WHO) told the press the new drugs were only part of the solution: “What will stop Ebola, under professor Muyembe’s leadership and that of the government of the DRC, is good surveillance, good infection prevention and control, good community engagement, excellent vaccinations, and the use of these therapeutics in the most effective way possible.”
Past EVD outbreak mortality rates have been at least 25%, as high as 90%, and averaged around 50% according to WHO’s statistics. According to Muyembe, many people do not seek treatment because they see their friends and relatives die after entering a care facility. “Now that 90% of their patients can go into the treatment center and come out completely cured,” he told the press, “they will start believing it and building trust in the population and community[.]”
Per the WHO’s Monitored Emergency Use of Unregistered and Investigational Interventions framework, all treatment centers in the DRC are to be permitted to administer mAb114 and REGN-EB3 to patients, even though research into the two treatments is not yet complete, and ZMapp and remdesivir are to be retired. A follow-on study, to be performed in the same four treatment centers as PALM, is to involve randomly assigning patients either a mAb114 or REGN-EB3 regimen.
In the DRC’s current Ebola outbreak, two thirds of those known to be infected with Ebola, over 1800 people, have died.