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

<p> Background <ul> <li> The Ebola virus disease (EVD) is a potentially fatal disease that is transmitted through close or direct contact through bodily fluids or blood </li> <li> The infection presents as an abrupt onset of fever and symptoms within days of exposure then progressing to severe bleeding and coagulation abnormalities </li> <li> 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&trade; (REGN-EB3, atoltivimab, maftivimab, and odesivimab) and Ebanga&trade; (MAb114, ansuvimab) </li> <li> The ebolavirus glycoprotein (GP) is targeted to produce antibodies against the Ebola virus; both treatments induce antibody-dependent cell cytotoxicity for the treatment of <em> Zaire ebolavirus </em> infection in adults and children </li> <li> Inmazeb&trade; is an antiviral drug combination of 3 recombinant human IgG1&kappa; monoclonal antibodies while Ebanga&trade; is a single <em> Zaire ebolavirus </em> glycoprotein (EBOV GP) </li> </ul></p><p> Objective <ul> <li> This review is intended to compare the efficacy and safety of the two recently FDA-approved therapies for EVD, Inmazeb&trade; and Ebanga&trade;, and their potential impact on breaking barriers of the disease and improving patient outcomes during inevitable future outbreaks </li> </ul></p><p> Methods <ul> <li> 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 </li> <li> The terms &ldquo;Inmazeb&rdquo;, &ldquo;Ebanga&rdquo;, &ldquo;MAb114&rdquo;, &ldquo;REGN-EB3&rdquo;, &ldquo;Ebola Virus&rdquo;, &ldquo;Ebola Virus Disease&rdquo;, &ldquo;Ebola Treatment&rdquo;, &ldquo;Ebola Antivirals&rdquo;, and &ldquo;Ebola Monoclonal Antibodies&rdquo; were utilized to conduct a systematic literature search </li> <li> Scientific databases used: PubMed, Ovid MEDLINE, The New England Journal of Medicine, ScienceDirect, Google Scholar databases, and ClinicalTrials.gov </li> <li> After screening the search results at the title and abstract level, the full texts of the selected papers were extracted for detailed analysis </li> <li> 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 </li> </ul></p><p> Results</p><p> <em> Trial Design </em> <ul> <li> A randomized, controlled trial was conducted on four investigational therapies for EVD in the Democratic Republic of Congo </li> </ul></p><p> <em> Enrollment </em> <ul> <li> Patients of any age who had a positive result for Ebola virus </li> <li> A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019 </li> </ul></p><p> <em> Intervention </em> <ul> <li> 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 </li> </ul></p><p> <em> Primary Endpoint </em> <ul> <li> Death at 28 days </li> </ul></p><p> <em> Results </em> <ul> <li> 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) </li> <li> 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) </li> <li> 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 </li> </ul></p><p> Summary <ul> <li> The clinical trial evaluated showed that both Inmazeb&trade; and Ebanga&trade; are superior to the control in reducing mortality with reliable efficacy concerning treatment for EVD </li> <li> Benefits of surviving were seen with both agents and observed in low as well as high viral loads at presentation </li> <li> Ongoing trials are conducted to assess the safety and pharmacokinetics of Inmazeb&trade; and Ebanga&trade;, as there is currently no data available to determine their effect on age, kidney disease, or hepatic impairment </li> <li> Additionally, the results showed the importance of early diagnosis and treatment signifying that a longer duration of symptoms before treatment resulted in worse outcomes </li> <li> 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 </li> <li> A limitation noted for both treatments is the efficacy; the clinical trial investigated the treatment of the <em> Zaire ebolavirus </em> , but these agents have not been tested for other species of the <em> Ebolavirus </em> and <em> Marburgvirus </em> genera </li> <li> Factors such as resistance or changes in viral virulence should be considered when determining drug therapy options as <em> Zaire ebolavirus </em> strains can change over time </li> </ul></p>