Ansuvimab
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Human |
Target | Zaire ebolavirus |
Clinical data | |
Trade names | Ebanga |
Other names | Ansuvimab-zykl, mAb114 |
License data | |
Intravenous | |
Drug class | Monoclonal antibody |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6368H9924N1724O1994S44 |
Molar mass | 143950.15 g·mol−1 |
Ansuvimab, sold under the brand name Ebanga, is a monoclonal antibody medication for the treatment of Zaire ebolavirus (Ebolavirus) infection.[1][2]
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.[1]
Ansuvimab was approved for medical use in the United States in December 2020.[1][2][3] It is on the World Health Organization's List of Essential Medicines.[4]
Chemistry
The drug is composed of a single
Mechanism of action
Neutralization
Ansuvimab is a
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.[5] Other functional killing tests have not been performed.[citation needed]
History
Ansuvimab is a
In 2018, a
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
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.[3] The trial enrolled newborn, pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection.[3] All participants received standard, supportive care for the disease.[3] 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).[3] The participants and the health care providers knew which treatment was being given.[3] The trial was conducted at four sites in the Democratic Republic of Congo during an outbreak that began in August 2018.[3]
Discovery
A 2016 paper describes the efforts of how ansuvimab was originally developed as part of research efforts led by Dr. Nancy Sullivan at the United States
Ansuvimab and mAb100 combination
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.[5]
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.[5] 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.[7][6]
Development
Ansuvimab was developed by the Vaccine Research Center with support of the United States National Institutes of Health and the Defense Advanced Projects Agency. The heavy and light chain sequences of ansuvimab mAb were cloned into CHO cell lines to enable large-scale production of antibody product for use in humans.[6][7]
Human safety testing
In early 2018,[11] a Phase 1 clinical trial of ansuvimab's safety, tolerability and pharmacokinetics was conducted by Dr. Martin Gaudinski within the Vaccine Research Center Clinical Trials Program that is led by Dr. Julie E. Ledgerwood.[7][6][13] The study was performed in the United States at the NIH Clinical Center and tested single dose infusions of ansuvimab infused over 30 minutes. The study showed that ansuvimab was safe, had minimal side effects and had a half-life of 24 days.[7][6]
Ridgeback Biotherapeutics
A license for ansuvimab was obtained by Ridgeback Biotherapeutics in 2018, from the National Institutes of Health-National Institute of Allergy and Infectious Diseases.[17] Ansuvimab was given orphan drug status in May 2019 and March 2020.[18][19][20]
Experimental use in the Democratic Republic of Congo
During the
Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in
In October 2020, the U.S. Food and Drug Administration (FDA) approved atoltivimab/maftivimab/odesivimab (Inmazeb, formerly REGN-EB3) with an indication for the treatment of infection caused by Zaire ebolavirus.[25]
References
- ^ a b c d "FDA Approves Treatment for Ebola Virus". U.S. Food and Drug Administration. 21 December 2020. Retrieved 23 December 2020. This article incorporates text from this source, which is in the public domain.
- ^ a b "Ridgeback Biotherapeutics LP Announces the Approval of Ebanga for Ebola" (Press release). Ridgeback Biotherapeutics LP. 22 December 2020. Retrieved 23 December 2020 – via Business Wire.
- ^ a b c d e f g "Drug Trials Snapshot: Ebanga". U.S. Food and Drug Administration (FDA). 21 December 2020. Retrieved 13 January 2021. This article incorporates text from this source, which is in the public domain.
- hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
- ^ PMID 26917593.
- ^ a b c d e f Clinical 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
- ^ PMID 30686586.
- ^ PMID 26917592.
- PMID 21866101.
- PMID 21866103.
- ^ a b "NIH begins testing Ebola treatment in early-stage trial". National Institutes of Health (NIH). 2018-05-23. Retrieved 2018-10-15.
- ^ S2CID 211835755.
- ^ a b c d e "NIH VideoCast - CC Grand Rounds: Response to an Outbreak: Ebola Virus Monoclonal Antibody (mAb114) Rapid Clinical Development". videocast.nih.gov. 13 March 2019. Retrieved 2019-08-09.
- ^ a b Kingsley-Hall A. "Congo's experimental mAb114 Ebola treatment appears successful: authorities | Central Africa". www.theafricareport.com. Retrieved 2018-10-15.
- ^ McNeil DG (12 August 2019). "A Cure for Ebola? Two New Treatments Prove Highly Effective in Congo". The New York Times. Retrieved 13 August 2019.
- ^ Molteni M (12 August 2019). "Ebola is Now Curable. Here's How The New Treatments Work". Wired. Retrieved 13 August 2019.
- ^ "Ridgeback Biotherapeutics LP announces licensing of mAb114, an experimental Ebola treatment, from the National Institute of Allergy and Infectious Diseases" (Press release). Ridgeback Biotherapeutics LP. Retrieved 2019-08-17 – via PR Newswire.
- ^ "Ansuvimab Orphan Drug Designations and Approvals". accessdata.fda.gov. 8 May 2019. Retrieved 24 December 2020.
- ^ "Ansuvimab Orphan Drug Designations and Approvals". accessdata.fda.gov. 30 March 2020. Retrieved 24 December 2020.
- ^ "Ridgeback Biotherapeutics LP Announces Orphan Drug Designation for mAb114" (Press release). Ridgeback Biotherapeutics LP. Retrieved 2019-08-17 – via PR Newswire.
- PMID 29789732.
- ^ "WHO: Consultation on Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus Disease" (PDF). who.int. World Health Organization. May 17, 2018. Retrieved November 2, 2021.
- ^ Mole B (2019-08-13). "Two Ebola drugs boost survival rates, according to early trial data". Ars Technica. Retrieved 2019-08-17.
- ^ "Independent monitoring board recommends early termination of Ebola therapeutics trial in DRC because of favorable results with two of four candidates". National Institutes of Health (NIH). 2019-08-12. Retrieved 2019-08-17.
- ^ "FDA Approves First Treatment for Ebola Virus". U.S. Food and Drug Administration (FDA) (Press release). 14 October 2020. Retrieved 14 October 2020. This article incorporates text from this source, which is in the public domain.
External links
- Clinical trial number NCT03719586 for "Investigational Therapeutics for the Treatment of People With Ebola Virus Disease" at ClinicalTrials.gov