Atoltivimab/maftivimab/odesivimab was evaluated in 382 adult and pediatric participants with confirmed Zaire ebolavirus infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018/2019. In the PALM trial, the safety and efficacy of atoltivimab/maftivimab/odesivimab was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 participants received atoltivimab/maftivimab/odesivimab (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 participants received an investigational control. The trial enrolled pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection. All participants received standard, supportive care for the disease. The participants and the health care providers knew which treatment was being given. The primary efficacy endpoint was 28-day mortality. The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab/maftivimab/odesivimab or the investigational control during the same time period of the trial. Of the 154 participants who received atoltivimab/maftivimab/odesivimab, 33.8% died after 28 days, compared to 51% of the 153 participants who received a control. In the expanded access program, an additional 228 participants received atoltivimab/maftivimab/odesivimab. Regulatory status
The FDA granted the application of atoltivimab/maftivimab/odesivimab-ebgn orphan drug and breakthrough therapy designations. The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an indication for the treatment of infection caused by Zaire ebolavirus in October 2020.The drug has also received orphan drug designation from the European Medicines Agency. References
Further reading
External links
"Atoltivimab". Drug Information Portal. U.S. National Library of Medicine.
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.