A clinical trial testing experimental Ebola treatments in the Democratic Republic of Congo was stopped early after results showed drugs from Regeneron Pharmaceuticals Inc. and the U.S. National Institutes of Health were superior to the control treatment, Mapp Biopharmaceutical's ZMapp.
The preliminary results of 499 patients in the Pamoja Tulinde Maisha, or PALM, Ebola study indicated that those who received Regeneron's REGN-EB3 or the NIH's mAb114 had a greater chance of surviving Ebola — a highly deadly infectious disease — versus study participants in the trial's other two arms.
NIAID Director Anthony Fauci
REGN-EB3 and mAb114 will be carried forward in the study's extension phase, but ZMapp and another experimental product from Gilead Sciences Inc., remdesivir, will be dropped from the trial, NIH's Anthony Fauci told reporters, saying the latter two drugs are "out of the picture."
Fauci, the longtime head of the NIH's National Institute of Allergy and Infectious Diseases, emphasized the results are preliminary.
"Not all the data has yet been accumulated," Fauci told reporters. "The only thing that is sure is that the two monoclonal antibodies — mAb114 and Regeneron's — are clearly better than ZMapp and remdesivir."
While the survival data was good, Fauci said the viral load results for REGN-EB3 and mAb114 were "very impressive."
He noted that the results from Regeneron's drug triggered the early termination of the study, but the data were "very close" for the NIH's mAb114 and there was no current major distinction between the two experimental drugs in the trial, so the data safety monitoring board decided to have both products continue in the extension study.
Regeneron's REGN-EB3 is a cocktail of three monoclonal antibodies. The company invented it using its VelociSuite technologies. The experimental product is being developed with funding from the U.S. Biomedical Advanced Research and Development Authority.
NIH's mAb114 consists of a single experimental monoclonal antibody that was isolated from a survivor of the 1995 Ebola epidemic in the DRC. The investigational product binds to the core of a surface protein on Ebola, blocking its interactions with a receptor on human cells and preventing the virus from entering and infecting them.
The NIH's Vaccine Research Center developed mAb114 under a partnership with the U.S. Army Medical Research Institute of Infectious Diseases and the Defense Advanced Research Projects Agency.
Fauci noted that the NIH licensed the development rights for mAb114 to Ridgeback Biotherapeutics LP, a Coconut Grove, Fla.-based biotech company.
Mapp's ZMapp is also a cocktail of three monoclonal antibodies, while Gilead's drug remdesivir, also known as GS-5734, is an antiviral.
ZMapp was used as the control arm in the PALM trial because of the results from the PREVAIL 2 clinical trial, a multicenter treatment study launched in March 2015 in the U.S. and West Africa. Final results of the PREVAIL 2 study reported in October 2016 indicated that ZMapp was safe and well-tolerated and showed a trend toward benefit. But because the Ebola epidemic in West Africa eventually subsided, the study enrolled too few people to determine definitively whether ZMapp was a better treatment for Ebola than supportive care alone, according to the NIH.
The PALM study was launched in November 2018 in the DRC as part of the emergency response to an ongoing Ebola outbreak in the North Kivu and Ituri provinces, officials noted. As of Aug. 9, the trial had enrolled 681 patients, with the goal of having 725 participants total, Fauci said.
"We are moved to know our therapy is helping save the lives of people facing this deadly infectious disease," Neil Stahl, executive vice president of research and development at Regeneron, said in an Aug. 12 statement.
Over 2,800 people in the DRC have been infected with Ebola, which has killed almost 1,900 since the current outbreak was declared Aug. 1, 2018.
Healthcare workers addressing the Ebola crisis
On July 17, the World Health Organization declared the outbreak a public health emergency of international concern after a person in Goma — a city of about 2 million people that borders Rwanda — was diagnosed as having the virus.
Healthcare workers in the DRC are facing a particularly difficult situation of trying to address the Ebola outbreak in the midst of active armed conflict in a densely populated area, officials noted.
Regeneron and the NIH are expected to have sufficient quantities of their experimental products to supply the extension trial and treat patients in the DRC during the current outbreak, Fauci said.
He noted the experimental treatments could not have been possible without the early discoveries of the use of antibodies in Ebola by Jean-Jacques Muyembe-Tamfum, director-general of the DRC's Institut National de Recherche Biomédicale, who told reporters he was "very happy" about the preliminary results.
Muyembe, Fauci said, is a "true hero."
While the results of the two experimental drugs were "fantastic," and healthcare workers in the DRC now have new tools to fight Ebola, ending the outbreak will take good surveillance, infection prevention and control, community engagement, vaccination, and effective use of the new products, said Mike Ryan, executive director of the World Health Organization's Health Emergencies Program.
"It's not one answer. It's many things," Ryan said. "But we've taken a huge step today."