Ansuvimab, sold under the brand name Ebanga, is a monoclonal antibody medication used for the treatment of Zaire ebolavirus (Ebolavirus) infection.[2][3]
The most common symptoms include fever, tachycardia (fast heart rate), diarrhea, vomiting, hypotension (low blood pressure), tachypnea (fast breathing) and chills; however, these are also common symptoms of Ebolavirus infection.[2]
Ansuvimab is a monoclonal antibody therapy that is infused intravenously into people with Ebola virus disease. Ansuvimab is a neutralizing antibody,[6] meaning it binds to a protein on the surface of Ebola virus that is required to infect cells. Specifically, ansuvimab neutralizes infection by binding to a region of the Ebola virus envelope glycoprotein that, in the absence of ansuvimab, would interact with virus's cell receptor protein, Niemann-Pick C1 (NPC1).[9][10][11] This "competition" by ansuvimab prevents Ebola virus from binding to NPC1 and "neutralizes" the virus's ability to infect the targeted cell.[9]
Effector function
Antibodies have antigen-binding fragment (Fab) regions and constant fragment (Fc) regions. The Neutralization of virus infection occurs when the Fab regions of antibodies binds to virus antigen(s) in a manner that blocks infection. Antibodies are also able to "kill" virus particles directly and/or kill infected cells using antibody-mediated "effector functions" such as opsonization, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent phagocytosis. These effector functions are contained in the Fc region of antibodies, but is also dependent on binding of the Fab region to antigen. Effector functions also require the use of complement proteins in serum or Fc-receptor on cell membranes. Ansuvimab has been found to be capable of killing cells by antibody-dependent cell-mediated cytotoxicity.[6]
Ansuvimab has also shown success with lowering the mortality rate from ~70% to about 34%. In August 2019, Congolese health authorities, the World Health Organization, and the U.S. National Institutes of Health promoted the use of ansuvimab, alongside atoltivimab/maftivimab/odesivimab, a similar Regeneron-produced monoclonal antibody treatment, over other treatments yielding higher mortality rates, after ending clinical trials during the outbreak.[16][17]
The U.S. Food and Drug Administration (FDA) approved ansuvimab based primarily on evidence from a clinical trial (Trial 1/ NCT NCT03719586) of 342 participants with Zaire ebolavirus infection.[4] The trial enrolled newborn, pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection.[4] All participants received standard, supportive care for the disease.[4] In addition to the standard care, participants were randomly assigned to receive either a one-time dose of ansuvimab or one of the three other types of experimental treatments (including one as the control group).[4] The participants and the health care providers knew which treatment was being given.[4] The trial was conducted at four sites in the Democratic Republic of Congo during an outbreak that began in August 2018.[4]
In an experiment described in the 2016 paper, rhesus macaques were infected with Ebola virus and treated with a combination of ansuvimab and another antibody isolated from the same subject, mAb100. Three doses of the combination were given once a day starting 1 day after the animals were infected. The control animal died and the treated animals all survived.[6]
Ansuvimab monotherapy
In a second experiment described in the 2016 paper, rhesus macaques were infected with Ebola virus and only treated with ansuvimab. Three doses of ansuvimab were given once a day starting 1 day or 5 days after the animals were infected. The control animals died and the treated animals all survived.[6] Unpublished data referred to in a publication of the 2018 Phase I clinical trial results of ansuvimab, reported that a single infusion of ansuvimab provided full protection of rhesus macaques and was the basis of the dosing used for human studies.[8][7]
Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in Kivu in the DRC (2018–20 Kivu Ebola outbreak). Once again, ansuvimab received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many people under these protocols.[14] In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing ansuvimab, atoltivimab/maftivimab/odesivimab (REGN-EB3) and remdesivir to ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators enrolled 681 participants towards their goal of 725. An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 participants found that ansuvimab and REGN-EB3 were superior to the comparator ZMapp. Overall mortality of participants in the ZMapp and remdesivir groups were 49% and 53% compared to 34% and 29% for ansuvimab and REGN-EB3. When looking at participants who arrived early after disease symptoms appeared, survival was 89% for ansuvimab and 94% for REGN-EB3. While the study was not powered to determine whether there is any difference between REGN-EB3 and ansuvimab, the survival difference between those 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 people in the outbreak who elect to participate in the trial will now be given either ansuvimab or REGN-EB3.[24][25][16][15]
^World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^ abcdefClinical trial number NCT03478891 for "Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-EBOMAB092-00-AB (MAb114), Administered Intravenously to Healthy Adults" at ClinicalTrials.gov
