Assessing vital therapies for Ebola in the midst of an outbreak

2019

Challenge

The suffering and death caused by two recent, major outbreaks of the Ebola virus, which causes a serious and often fatal illness marked by fever and bleeding, highlights the need for randomized, controlled trials of promising experimental treatments. There are currently no licensed antiviral drugs or antibodies available to treat Ebola, so physicians currently can only help patients by managing their symptoms.  

Advance

An international partnership of scientists, clinicians, and healthcare workers conducted a trial of four investigational therapies for Ebola virus infection in the Democratic Republic of Congo. Patients with Ebola received standard care and were also randomly assigned one of the therapeutics: the triple monoclonal antibody ZMapp; the antiviral agent remdesivir; the triple monoclonal antibody REGN-EB3; or the single monoclonal antibody mAb114, which was developed through a collaboration between IRP researchers led by senior investigator Clifford Lane, M.D., and scientists at the Democratic Republic of Congo’s Institut National de Recherche Biomédicale. The study, part of a clinical trial known as Pamoja Tulinde Maisha (PALM), which means “Together Save Lives” in the Kiswahili language, was halted early because both mAb114 and REGN-EB3 were found to be superior to ZMapp at preventing death from Ebola.

Impact

The PALM trial provided compelling support for the use of mAb114 and REGN-EB3 in the fight against Ebola. Moreover, while survival benefits were seen in patients with both large and small amounts of the virus in their bodies, the study underscored the importance of seeking early clinical care after onset of symptoms, as the odds of death from Ebola increased 11 percent each day that a person delayed going to a treatment center. Finally, the PALM trial demonstrated that scientifically rigorous and ethically sound clinical research can be conducted during disease outbreaks.

Publications

Mulangu S, Dodd LE, Davey RT, Tshiani Mbaya O, Proschan M, Mukadi D, Lusakibanza Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC, Grais R, Diaz J, Lane HC, Muyembe-Tamfun JJ, PALM Writing Group, Sivahera B, Camara M, Kojan R, Walker R, Dighero-Kemp B, Cao H, Mukumbayi P, Mbala-Kingebeni P, Ahuka S, Albert S, Bonett T, Crozier I, Duvenhage M, Poffitt C, Teitelbaum M, Moench T, Aboulhab J, Barrett K, Cahill K, Cone K, Eckes R, Hensley L, Herpin B, Higgs E, Ledgerwood J, Pierson J, Smolskis M, Sow Y, Tierney J, Sivapalasingam, Holman W, Gettinger N, Vallée D, Nordwall J, PALM Consortium Study Team. (2019). A randomized controlled trial of Ebola virus disease therapeutics. New Engl. J. Med. Dec 12;381(24):2293-2303.