Two monoclonal treatment treatments for Ebola related to a much lower mortality rate among patients with the virus in the Democratic Republic of Congo, a random trial was found.
The single monochrome antibody MAb114 and a monoclonal tripartite antibody provided lower death rates after 28 days compared to the modern contraceptive agent in development for Ebola and compared with the other monoclonal antibody, ZMapp, which showed a promise in a trial. other.
In fact, 35.1% of patients on MAb114 and 33.5% of the REGN-EB3 group had died after 28 days compared to 49.7% of patients in the redesigned group and 51.3% d & # 39; patients in the ZMapp group, H. Clifford Lane, MD, the Institute of Allergy and Infectious Diseases (NIAID), and colleagues in the Gaeltacht reported New England Medical Journal.
The NIAID announced these previous results in August, when an independent Board for Safety and Data Monitoring said the trial should be stopped soon and patients should be treated with REGN-EB3 Regeneron or MAb114 treatment, which The agency developed itself.
Moreover, the board recommended that any person treated with Ebola should be given the option of making these two monoclonal antibody therapy at the discretion of the doctor.
"Closing endorsement is this cut results to randomized clinical trials … and provides options based on scientific data to determine the best intervention," said NIAID director, Anthony Fauci, MD, in August.
The authors noted that almost all deaths occurred within 10 days of enrollment, and that REGN-EB3 and MAb114 patients had faster viral clearance rates compared to the remdesivir and ZMapp groups. They noted that only two doses were required from the two previous treatments, although the last two required multiple infusions as a possible cause for the differences.
Accompaniment editing by Myron Levine, MD, of the University of Maryland in Baltimore, has noted many differences between the two treatments. REGN-EB3 was obtained by immunising mice incorporating human antibody segments that fully generate human antibodies, and derived MAb114 from surviving Ebola patient cells. But both had success in pre-clinical studies.
"MAb114 and REGN-EB3 have been shown to reduce mortality among non-human primates in control challenge studies with t Z. evolavirus song, "Levine wrote.
In the Pamoja Tulinde Maisha (Swahili for "save lives together"), or PALM trial, Lane and colleagues included patients who tested positive for Ebola RNA, including pregnant women.
The 673 participants were assigned to get remdesivir, MAb114, REGN-EB3, or ZMapp as a control. The trial was first designed in November 2018 with three groups. REGN-EB3 was discontinued late in January 2019.
Approximately three quarters of patients were adults, with the remainder divided between 6-17 and those aged 5 and under. More than half the patients were women, and about 6% were pregnant when the diagnosis was made. Patients were registered within at least 6 days after diagnosis.
Vaccination information was available to 620 patients. Among the quarter who said they received the Ebola vaccine, 39% said they had received at least 10 days before registering in the study.
An interim efficiency analysis was carried out on 499 patients in August 2019, when REGN-EB3 found that an efficiency threshold had been crossed by the NIAID in August. They also received a "clear separation" between REGN-EB3 and MAb114 and remdesivir and ZMapp.
Overall, the death occurred in 43% of patients by day 28 – about 13% with low viral load and 77% with high viral load.
Death rates were 14.6 lower points with MAb114 than ZMapp (P= 0.007) and 17.8 percentage points lower with REGN-EB3 than ZMapp (P= 0.002). However, there was only a significant 3.4-percentage difference between remdesivir and ZMapp (95% CI -7.2 to 14.0).
Examination of safety, there were 29 serious adverse events, but three patients involved in the study drug were not considered to have four incidents:
- One in ZMapp group and GI signals to slide
- Head in the ZMapp group with hypotectivity and hypoxia infertile leading to death within 24 hours
- One in the reaffirmed group with an hypothesis that resulted in cardiac end
While all of these patients died, the authors noted that the cause of death could not be determined as the adverse event or the Ebola infection itself.
Levine said that these treatments are "very promising" that the cost, the number of possible desks, and the target population should be explored. " While certain issues remain, such as the product "which would be more suitable for economically viable large-scale production," he said.
"One product based on monochrome antibody has a number of advantages. It would be desirable to obtain a stockpile of both products if licensed," wrote Levine.
The study was primarily supported by the National Institute for Allergy and Infectious Diseases (NIAID).
The Democratic Republic of Congo provided additional support and the African Alliance for Epidemic Research, Response and Training.
The ZMapp production was supported by the US Department of Health and Human Services Biomedical and Advanced Research and Development Authority.
The production of MAb114 was supported by NIAID and the US Department of Defense.
Mapp Biopharmaceutical provided for ZMapp, removivir was provided by Gilead Sciences, NIAID MAb114 was provided, and Regeneron Pharmaceuticals provided support for the provision of REGN-EB3.
Lane revealed no conflicts of interest.
Other co-authors show support from Gilead Sciences, Ridgeback Biotherapeutics, Bippharmaceutical Mapp, and BARDA.
A number of patented authors disclosed the neutralization of antibodies to the Ebola virus glycoprotein.
One co-author disclosed a patent on MAb114 for Ebola treatment licensed to Ridgeback and another private entity.
Levine did not disclose any conflicts of interest.
2019-11-27T17: 00: 00-0500