Atoltivimab/maftivimab/odesivimab, sold under the brand name Inmazeb, is a fixed-dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus (Ebola virus). It contains atoltivimab, maftivimab, and odesivimab-ebgn and was developed by Regeneron Pharmaceuticals.The most common side effects include fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting; however, these are also common symptoms of Ebola virus infection.Atoltivimab/maftivimab/odesivimab is the first FDA-approved treatment for Zaire ebolavirus. Atoltivimab/maftivimab/odesivimab was approved for medical use in the United States in October 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses
Atoltivimab/maftivimab/odesivimab is indicated for the treatment of infection caused by Zaire ebolavirus. Contraindications
People who receive atoltivimab/maftivimab/odesivimab should avoid the concurrent administration of a live vaccine due to the treatments potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccines efficacy. Pharmacology
Mechanism of action
Atoltivimab/maftivimab/odesivimab is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies. The three antibodies target the glycoprotein that is on the surface of the Ebola virus. This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell. The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus.This combination drug targets the Zaire species of Ebola virus. The Sudan and Bundibugyo strains have also caused outbreaks, and it is unlikely that it would be effective against these strains.
History
Early development
The 2014 Ebola outbreak killed more than 11,300 people. Regeneron used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. governments Biomedical Advanced Research and Development Authority (BARDA). The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015. PALM trial
During the 2018 Équateur province Ebola outbreak, a similar monoclonal antibody treatment, mAb114, was requested by the Democratic Republic of Congo (DRC) Ministry of Public Health. 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. However, the outbreak came to a conclusion before any therapeutic agents were given to patients.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, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols. 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.