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

Location

Suwanee, GA

Start Date

3-5-2022 1:00 PM

End Date

3-5-2022 4:00 PM

Description

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 time

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COinS
 
May 3rd, 1:00 PM May 3rd, 4:00 PM

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

Suwanee, GA

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 time