Review of the New FDA-Approved Treatment Options for Ebola Virus Disease

Background The Ebola virus disease (EVD) is a potentially fatal disease that is transmitted through close or direct contact through bodily fluids or blood The infection presents as an abrupt onset of fever and symptoms within days of exposure then progressing to severe bleeding and coagulation abnormalities Although supportive measures have been the mainstay treatment, the U.S. Food and Drug Administration (FDA) approved two new treatments for the Ebola virus, Inmazeb™ (REGN-EB3, atoltivimab, maftivimab, and odesivimab) and Ebanga™ (MAb114, ansuvimab) The ebolavirus glycoprotein (GP) is targeted to produce antibodies against the Ebola virus; both treatments induce antibody-dependent cell cytotoxicity for the treatment of Zaire ebolavirus infection in adults and children Inmazeb™ is an antiviral drug combination of 3 recombinant human IgG1κ monoclonal antibodies while Ebanga™ is a single Zaire ebolavirus glycoprotein (EBOV GP) Objective This review is intended to compare the efficacy and safety of the two recently FDA-approved therapies for EVD, Inmazeb™ and Ebanga™, and their potential impact on breaking barriers of the disease and improving patient outcomes during inevitable future outbreaks Methods A drug review of treatments for EVD was completed through collecting and evaluating clinical trials and studies from 2019-2021 to assess the place in therapy The terms “Inmazeb”, “Ebanga”, “MAb114”, “REGN-EB3”, “Ebola Virus”, “Ebola Virus Disease”, “Ebola Treatment”, “Ebola Antivirals”, and “Ebola Monoclonal Antibodies” were utilized to conduct a systematic literature search Scientific databases used: PubMed, Ovid MEDLINE, The New England Journal of Medicine, ScienceDirect, Google Scholar databases, and ClinicalTrials.gov After screening the search results at the title and abstract level, the full texts of the selected papers were extracted for detailed analysis Six articles qualified and only two were selected to be included in this review; the four that were not selected was due to the lack of appropriateness and relevancy for the article, inconclusive findings, and/or flaws in the methodology based at the discretion of the reviewers Results Trial Design A randomized, controlled trial was conducted on four investigational therapies for EVD in the Democratic Republic of Congo Enrollment Patients of any age who had a positive result for Ebola virus A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019 Intervention All patients received standard care and were randomly assigned in a 1:1:1:1ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonalantibody MAb114, or the triple monoclonal antibody REGN-EB3 Primary Endpoint Death at 28 days Results At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P=0.007) At 28 days, death had occurred in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P=0.002) The odds of death increased by 11% (95% CI, 5 to 16) for each day after the onset of symptoms that the patient delayed treatment Summary The clinical trial evaluated showed that both Inmazeb™ and Ebanga™ are superior to the control in reducing mortality with reliable efficacy concerning treatment for EVD Benefits of surviving were seen with both agents and observed in low as well as high viral loads at presentation Ongoing trials are conducted to assess the safety and pharmacokinetics of Inmazeb™ and Ebanga™, as there is currently no data available to determine their effect on age, kidney disease, or hepatic impairment Additionally, the results showed the importance of early diagnosis and treatment signifying that a longer duration of symptoms before treatment resulted in worse outcomes Despite increased serum creatinine and aminotransferase levels in the ZMapp and remdesivir groups, patients still had better outcomes in the MAb114 and REGN-EB3 groups A limitation noted for both treatments is the efficacy; the clinical trial investigated the treatment of the Zaire ebolavirus, but these agents have not been tested for other species of the Ebolavirus and Marburgvirus genera Factors such as resistance or changes in viral virulence should be considered when determining drug therapy options as Zaire ebolavirus strains can change over tim