MAb114 and REGN-EB3 preferred over ZMapp and remdesivir for the treatment of Ebola virus disease (PALM)

Reference

Mulangu S, Dodd LE, Davey RT, et al, for the PALM Consortium Study Team. A randomized, controlled trial of ebola virus disease therapeutics. New Engl J Med 2019;381(24):2293-2303.

Synopsis

The first drug approved for the treatment of Ebola virus disease was ZMapp (a triple monoclonal antibody). Patients treated with ZMapp had 22% mortality in an earlier outbreak. Since then, several other therapies have been developed to treat Ebola virus disease, and these researchers decided to perform a randomized controlled trial during the next outbreak. In this study, patients given a diagnosis of Ebola virus disease during an outbreak beginning August 2018 were randomized to receive 1 of 3 treatments: (1) ZMapp, (2) remdesivir (a nucleotide analogue RNA polymerase inhibitor), or (3) MAb114 (a single monoclonal antibody). In January 2019 a fourth drug was added— REGN-EB3—and it was compared only with patients recruited after January 2019 who were assigned to the ZMapp group. That is because some characteristics of patients associated with mortality, such as days prior to initiation of therapy, may change as the outbreak evolves. The patient population consisted of 56% women and 75% adults, with a mean symptom duration of 5.5 days prior to enrollment. Approximately 25% had been vaccinated for Ebola prior to infection, most fewer than 10 days prior to admission. A total of 681 patients were enrolled before the study was halted. Groups were balanced and analysis was by intention to treat. The 28-day mortality rate was significantly lower for Mab114 than for ZMapp (35.1% vs 49.7%) and significantly lower for REGN-EB3 than for the subgroup of patients treated with ZMapp after January 2019 (33.5% vs 51.3%). Patients randomized to receive remdesivir had similar mortality to those who received ZMapp. The results were similar for patients with high and low viral loads, although the overall mortality was higher with higher viral loads.