Regeneron’s REGN-EB3 and a monoclonal antibody developed by the NIH called mAb114, both harvested from survivor’s of Ebola infections, show promise as treatments for the deadly Ebola virus. The treatments are now being offered to patients in the Democratic Republic of Congo (DRC) reports the National Institute of Allergy and Infectious Diseases.
Summary of Results Thus Far
NIH reports that both of these investigational treatments showed “clearly better” results in patients in a clinical trial of four potential treatments being conducted during the second-largest Ebola outbreak in history now in the second year in the DRC.
The PALM Trial
The PAmoja TuLinde Maisha (PALM [together save lives]) clinical trial was a randomized, multicenter, controlled trial to evaluate the safety and efficacy of four investigational agents for the treatment of patients with Ebola infection—including three antibody-based therapies, REGN-EB3, ZMapp and mAb114 (a single monoclonal antibody); and one small molecule antiviral, redeliver. The primary objective of the trial was to compare mortality in patients with Ebola who received either REGN-EB3, mAb114 or remdesivir to those who received ZMapp in the control arm. The National Institutes of Health (NIH) and the Institut National de Recherche Biomedicale (INRB) in the DRC sponsored and served as co-principal investigators.
Regeneron was notified by study investigators that the randomized, controlled trial evaluating four investigational therapies for Ebola virus infection was stopped early because REGN-EB3 was superior to ZMapp in preventing death. ZMapp served as the control arm of the trial because it was considered the standard-of-care based on the previous PREVAIL II clinical trial. The protocol specified that the PALM trial would only be stopped early for a highly statistically significant result. The independent data safety monitoring board decided to stop the trial after reviewing the interim mortality data from 499 patients. The trial was conducted in the DRC.
The study was first initiated in 2018 with three treatment arms including 1) mAB114, 2) remdesivir and 3) ZMapp. The trial protocol was amended after the World Health Organization (WHO) held an Ad-Hoc Expert Consultation to assess all preclinical and clinical data on available investigational products, and recommended the addition of REGN-EB3 as a fourth treatment arm.
What is REGN-EB3?
REGN-EB3 was invented by Regeneron using its VelociSuite® technologies; the therapy combines three fully-human monoclonal antibodies. REGN-EB3 has received orphan drug designation from both the FDA and the EMA. It is being developed, tested and manufactured as part of an agreement established in 2015 with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS). REGN-EB3 is currently under development and its safety and efficacy have not been fully evaluated by any regulatory authority.
What is mAb114?
mAb114 is a monoclonal antibody that is being evaluated as a treatment for Ebola virus disease. It is based on antibodies originally derived from the blood of a survivor of Ebola virus disease who contracted the disease in Kikwit in 1995. In early 2018, a Phase I clinical trial of mAb114 was conducted by the NIH Vaccine Research Center Clinical Trials Program led by Julie E. Ledgerwood. mAb114 is also being evaluated during the 2018 North Kivu Ebola outbreak (PALM trial).
mAb114 has shown great success in lowering the mortality rate from 90% to about 34%.
Anthony S. Fauci, MD NIAID
INRB Director-General Professor Jean-Jacques Muyembe-Tamfum, MD, PhD
Michael J. Ryan, MD, Executive Director, WHO Health Emergencies Programme