A research group today published full results from a clinical trial of four Ebola therapies in the Democratic Republic of the Congo (DRC) outbreak, in which preliminary findings in August led health officials to push the pause button to steer patients into groups to receive two treatments that stood out as most promising.
An international research group, which includes renowned Ebola researcher and DRC health official Jean-Jacques Muyembe-Tamfum, MD, published its findings in the New England Journal of Medicine (NEJM).
Study fleshes out preliminary findings
In August, an independent board that was monitoring the study in people treated in DRC Ebola treatment units took an early look at the data and saw that mortality rates were significantly lower in those who received the monoclonal antibody cocktail REGN-EB3 (made by Regeneron of Tarrytown, New York) and the single monoclonal antibody mAb 114, developed from antibodies of an Ebola survivor.
The other two therapies in the trial were the triple monoclonal antibody ZMapp, used as a control, and the antiviral drug remdesivir.
Patients in the study were randomized to receive one of the drugs, plus standard care. The trial began in November 2018 and enrolled 681 patients. To compare the four treatments, the researchers assessed their impact against death at 28 days.
Mortality was lower in the mAb114 group, 35.1%, compared with 49.7% in those who got ZMapp. For REGN-EB3, mortality was 33.5%, compared with 51.3% in a ZMapp subgroup. And for remdesivir, overall mortality was 53.1%
Results were even more impressive for patients who had low viral loads. The team identified four serious adverse events that were possibly related to the trial drugs.
The group concluded that both mAB114 and REGN-EB3 are superior to ZMapp in reducing death from Ebola and that it's possible to conduct ethically sound clinical research in an outbreak setting.
Implications for future outbreaks
In a related commentary in the same NEJM issue, Myron Levine, MD, DTPH, with the University of Maryland School of Medicine, wrote that the effects of the top two performing treatments are promising enough to explore the cost, number of doses that can be produced, and target populations for treatment.
A single monoclonal antibody-based treatment offers some advantages, he said, and it would be helpful to have stockpiles of both products if they are licensed.
Among the study's notable findings that Levine highlighted was the fact that the efficacy of the two drugs was greater in people who sought early treatment, had low viral loads, and markers for less severe illness.
Community engagement can influence patients to get early care, but Levine added that early care hinges on the availability of rapid diagnostics and the ease of travel to treatment centers, both issues that can enhance the impact of the two treatments and should be addressed in future outbreaks.
He praised the research team for their work conducting a randomized, controlled clinical trial under difficult conditions that included civil unrest and armed conflict. Levine also said the trial clearly shows a role for monoclonal antibodies in cutting Ebola deaths, which he said raises questions about their role in tamping down deaths in outbreaks involving other diseases, such as Middle East respiratory syndrome coronavirus (MERS-CoV).
Four DRC hot spots remain
No new Ebola cases were reported in the DRC today, keeping the outbreak total at 3,304 cases, according to numbers reflected on the World Health Organization (WHO) online Ebola dashboard. Health officials are still investigating 366 suspected cases, and the number of deaths held steady at 2,198.
The WHO's detailed weekly situation report on the outbreak yesterday said seven new cases in four health zones were reported for the week ending Nov 24, and four were in Mabalako. It said civil unrest prompted some Ebola responders to be relocated from Beni yesterday, but most remain in place to continue their activities. "The immediate focus will be on maintaining the safety and welfare of response personnel while preserving essential response activities in these places," the WHO said.
The group warned that violence in response areas could affect contact tracing, case management, and other activities in areas where virus transmission is still occurring.
Yesterday's daily report from the DRC's Ebola technical committee (CMRE) said that, despite the tension in Beni, a vaccination ring was opened around a case that was confirmed in late October.
MSF urges focus on wider health needs
Meanwhile, Doctors Without Borders (MSF) yesterday weighed in with its latest assessment on the outbreak, airing several concerns about the response and sharing the latest developments on its efforts.
MSF said many health workers have been recruited from health centers across the DRC, which stretches staffing and resources for non-Ebola medical needs throughout the country and further weakens the country's health system and affects how the community views the Ebola response. The organization said it strongly encourages donors to consider the country's wider needs, rather than just focusing on the Ebola response.
Though fewer cases have been confirmed over the past weeks, data show an average 5-day delay between symptom onset and diagnosis, a time when patients are infectious and miss receiving treatments that increase their chance of survival.
The group emphasized that the Ebola outbreak is only one of several pressing medical issues in the DRC, noting that only 4% of patients taken to treatment centers have tested positive for Ebola. It also repeated its concerns about a need to limit ring vaccination, instead highlighting possible benefits of a wider geographic approach, given contact tracing difficulties.
MSF said its staff in the DRC is adjusting to evolving hot spots. It has closed or downsized some centers, but is setting up new activities in other regions. One such area is Ituri, where the group is transforming a small facility into a 20-bed Ebola treatment center in the Biakato Mines area.
Nov 27 N Engl J Med abstract
Nov 27 N Engl J Med commentary
Aug 12 CIDRAP News story "Ebola outbreak treatment trial narrowed to two promising drugs"
WHO online Ebola dashboard
Nov 26 WHO Ebola situation report
Nov 26 CMRE report
Nov 26 MSF statement