By Stan Deresinski, MD, FACP, FIDSA, FESCMID
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Two monoclonal antibody preparations have been demonstrated to significantly reduce mortality in patients with Ebola virus infection.
SOURCE: Mulangu S, Dodd LE, Davey RT Jr, et al; PALM Consortium Study Team. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 2019;381:2293-2303.
In a study in the Democratic Republic of the Congo (DRC), patients with documented Ebola virus infection were randomized to one of four experimental intravenous therapies. These were ZMapp (a combination of three monoclonal antibodies), remdesivir (a nucleotide analog inhibitor of RNA polymerase), mAb114 (a monoclonal antibody derived from a survivor of Ebola), and REGN-EB3 (a mix of three human IgG1 monoclonal antibodies). The last arm was added to the trial partway through. Based on the negative results of a previous trial that found minimal benefit, ZMapp was considered to be a control arm.
The data safety monitoring board interrupted enrollment after 681 patients when an interim analysis found that mAb114 and REGN-EB3 were superior to the other two treatments with respect to mortality. Death at 28 days occurred in 61/174 (35.1%) and 52/155 (33.5%) in the MAb114 and REGN-EB3 groups, respectively, with each statistically superior to ZMapp. Remdesivir did not differ significantly from ZMapp. There was an 11% increase in the odds of death for each day of symptoms before trial enrollment. High baseline viral load, as well as elevated creatinine and alanine aminotransferase levels, also were associated with increased mortality.
The development of effective therapeutics for the treatment of Ebola virus infection is a triumph. The ability to overcome the obstacles to conducting this trial successfully in conflict-ridden DRC was nothing short of amazing. In addition, the demonstration of efficacy perhaps opens the door to treatment of other emerging virus infections. However, the downside is the cost of monoclonal antibody therapies and the need for intravenous administration. Despite their efficacy, approximately one-third of patients died. Fortunately, the recent development of an effective vaccine to prevent Ebola infection, if widely implemented, has the capability of reducing the number of future cases of this often-lethal disease.