REGN-EB3

Colorized scanning electron micrograph of Ebola virus particles (green)

REGN-EB3 is a cocktail of three monoclonal antibodies REGN3470, 3471 and 3479. It was invented by Regeneron using its VelociSuite® technologies.[1]

Using three antibodies targets the Ebola virus at multiple points since the virus is known to mutate in different outbreaks.[2]

Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope (the part of an antigen that is recognized by the antibody).

The 2014 Ebola outbreak killed more than 11,300 people. The company used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. government’s Biomedical Advanced Research and Development Authority (BARDA).[2] The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015. [2]

REGN-EB3 has received orphan drug designation from both the U.S. Food and Drug Administration and the European Medicines Agency.[1] REGN-EB3 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).[1]

REGN-EB3 is currently under clinical development and its safety and efficacy have not been fully evaluated by any regulatory authority.[1]

It was developed against the Zaire species of Ebola virus, but the Sudan and Bundibugyo strains have also caused outbreaks and it is unlikely that EB3 would be effective against these strains.[3]

EB3 is administered in a single dose and is stable enough to not need to be stored in a deep freeze.[2]

During the 2018 Équateur province Ebola outbreak, mAb114 was requested by the Democratic Republic of Congo (DRC) Ministry of Public Heath. mAb114 was approved for compassionate use by the World Health Organization MEURI ethical protocol and at DRC ethics board. mAb114 was sent along with other therapeutic agents to the outbreak sites.[4][5][6] However, the outbreak came to a conclusion before any therapeutic agents were given to patients.[6]

Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in Kivu in the DRC (2018-19 Kivu Ebola outbreak). Once again, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols.[6] In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing mAb114, REGN-EB3 and remdesivir to ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators have enrolled 681 patients towards their goal of 725.

This is the second worst ever outbreak and over 2,800 people are infected including 1,900 who have died.[7]

An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 patient found that mAb114 and REGN-EB3 were superior to the comparator ZMapp. Overall mortality of patients in the ZMapp and Remdesivir groups were 49% and 53% compared to 34% and 29% for mAb114 and REGN-EB3. When looking at patients who arrived early after disease symptoms appeared, survival was 89% for mAB114 and 94% for REGN-EB3. While the study was not powered to determine if there is a true difference between REGN-EB3 and mAb114, the survival difference between the two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN-EB3.[8][9][10][11]

In August 2019, Congolese health officials announced it was more effective compared to two other treatments being used at the time.[12][10][13]

Among patients treated with it, 34% died; the mortality rate improved if the drug was administered soon after infection, in a timely diagnosis- critical for those infected with dangerous diseases like Ebola that can cause sepsis and, eventually, multiple organ dysfunction syndrome, more quickly than other diseases. This makes Ebola potentially a treatable disease.[14] The survival rate if the drug was administered shortly after infection was 90%.[7]