An early halt to a clinical trial examining four potential Ebola therapies in the Democratic Republic of the Congo (DRC) was recommended, as two monoclonal antibody treatments were clearly more effective in an interim analysis, researchers said.
An independent Data Safety and Monitoring Board recommended that the Pamoja Tulinde Maisha (Swahili for "together save lives") or PALM trial should be terminated early, and that Ebola patients should receive treatment with either Regeneron's REGN-EB3 (a cocktail of three monoclonal antibodies) or mAb114, which was developed by the National Institute of Allergy and Infectious Diseases (NIAID).
In addition, Ebola patients who were randomized to either ZMapp (the control treatment) or the nucleoside analog remdesivir in the last 10 days would have the option to receive either of the two monoclonal antibody therapies, per the discretion of their treating physician.
On a conference call with reporters, NIAID Director Anthony Fauci, MD, explained that REGN-EB3 "crossed a threshold of efficacy that would halt the study."
But he added that the difference between REGN-EB3 and mAb114 was small enough to proceed with these two therapies in an extension study.
"These clear-cut findings are a ringing endorsement to conduct randomized clinical trials ... and provide options based on scientific data to determine the best intervention," Fauci said. "[These] core principles of science and ethics in conducting clinical research should not change during an epidemic."
Michael Ryan, MD, executive director of the World Health Organization (WHO) Health Emergencies Program, said that the WHO "welcomed the results of the study." He added that over 100 people are inpatients in a large number of Ebola treatment units, and that while those who reach care early have had "outstanding results," not enough people are getting treatment fast enough.
"Getting people into care more quickly is vital for increasing survival," Ryan said, adding that the median time between the onset of a case and admission to an Ebola treatment center has gone from 5-6 days to about 4 days, but there is still a "wide range of delays for admission" and patients are still staying too long in the community.
"This gives us a new toolbox in the fight against Ebola, but it doesn't stop Ebola," Ryan added.
Most recently, indicated there were 2,781 cases of Ebola in this current outbreak, and 1,886 deaths.
PALM was an ongoing clinical trial of four Ebola therapeutics, including ZMapp as a control. PALM had enrolled 681 participants at four Ebola treatment centers in four Ebola hotspots in the DRC -- Beni, Katwa, Butembo, and Mangina. The trial had a target of 725 patients for enrollment, but the recommendation to stop the trial was after a review of data from 499 patients, Fauci said.
Indeed, the findings were not close. Fauci noted that overall mortality was much higher in the remdesivir and ZMapp arms compared with the two monoclonal antibody treatments:
- Remdesivir: 53%
- ZMapp: 49%
- mAb114: 34%
- REGN-EB3: 29%
The researchers found that these mortality numbers were even stronger among Ebola patients with a low viral load -- meaning the patients who came in for treatment early (33%, 24%, 11%, and 6%, respectively).
But when asked why researchers wouldn't continue the treatment with just REGN-EB3, Fauci emphasized that these were preliminary results only.
"Any determination to fine-tune for one versus the other is premature at this time," he said.
Data from the initial study will be analyzed after the data are generated and collected, likely this fall. , the NIAID said that the results will then be submitted for publication in the peer-reviewed medical literature "as quickly as possible."