The full results of a clinical trail of four experimental Ebola treatments that was initially stopped early due to positive results have been released.
The PALM trial (short for the Swahili expression pamoja tulinde maisha, which means “together save lives”) evaluated three Ebola antibody preparations and one antiviral drug in a randomized controlled trial conducted in the midst of the yearlong outbreak in the Democratic Republic of the Congo (DRC) that has already claimed the lives of nearly 2,000 people. PALM began in November 2018 and ran through August 2019 when a safety monitoring board reviewed data for 499 patients and found the triple monoclonal antibody REGN-EB3 to be superior to ZMapp, which was the control group. Treatments were made widely available immediately.
ZMapp, also a triple monoclonal antibody, was first used during the 2014 West Africa Ebola outbreak, having only been previously tested on animals and not yet subjected to a randomized controlled trial. At the time, no other drugs were available to treat the virus and the World Health Organization gave its support. Once hailed as a savior, a 2016 trial of ZMapp did not show a significant effect on mortality.
The current study comprising 673 patients was designed to compare mortality rates between those who received one of the three investigational drugs with those from the control group who received ZMapp. The other therapies include mAb114 (a single monoclonal antibody), remdesivir (an antiviral drug) and REGN-EB3 (a monoclonal antibody cocktail). The trial was amended to include REGN-EB3 two months after launch (January 2019).
Overall, the mortality rate was:
- 50 percent in all patients treated with ZMapp
- 51 percent in patients who received ZMapp post-January
- 35 percent in patients who were treated with mAb114
- 34 percent in those treated with REGN-EB3
- 53 percent in patients who received remdesivir
Analysis showed that patients who received either mAb114 or REGN-EB3 cleared the virus from their blood more quickly than patients who were treated with ZMapp. The study leaders—Jean-Jacques Muyembe-Tamfum, M.D., director-general of the INRB and head of the DRC's Ebola response, and Richard Davey, Jr., M.D., deputy director of NIAID's Division of Clinical Research—also noted how critical early diagnosis and treatment is, having a profound impact on mortality rates. For example, patients who arrived at a treatment center within one day of reported onset of symptoms had a mortality rate of 19 percent, while patients who arrived after five days of symptoms had a mortality rate of 47 percent. The odds of death increased 11 percent each day a patient delayed treatment after initial symptoms.
"These results bring more than hope, they show what powerful tools we have now to save lives in the Democratic Republic of the Congo, and in future Ebola outbreaks. We must make sure everyone affected by the virus knows about these treatments and is able to access them," said WHO Director-General, Dr. Tedros Adhanom Ghebreyesus.
Importantly, the results also demonstrate that sound scientific research can indeed be implemented during disease outbreaks—something that was not achieved during the 2014 West African Ebola epidemic.
Photo: An Army researcher sets up an assay for Ebola within a containment laboratory in West Africa in 2014. Credit: Dr. Randal J. Schoepp