title: Efficacy and safety of AVP-21D9, an anthrax monoclonal antibody, in animal models and humans.
abstract: Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. However, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. An anthrax antitoxin, AVP-21D9, also known as Thravixa (fully human anthrax monoclonal antibody), is being developed as a therapeutic agent against anthrax toxemia. The efficacy of AVP-21D9 in B. anthracis-infected New Zealand White rabbits and in cynomolgus macaques was evaluated, and its safety and pharmacokinetics were assessed in healthy human volunteers. The estimated mean elimination half-life values of AVP-21D9 in surviving anthrax-challenged rabbits and nonhuman primates (NHPs) ranged from approximately 2 to 4 days and 6 to 11 days, respectively. In healthy humans, the mean elimination half-life was in the range of 20 to 27 days. Dose proportionality was observed for the maximum serum concentration (Cmax) of AVP-21D9 and the area under the concentration-time curve (AUC). In therapeutic efficacy animal models, treatment with AVP-21D9 resulted in survival of up to 92% of the rabbits and up to 67% of the macaques. Single infusions of AVP-21D9 were well tolerated in healthy adult volunteers across all doses evaluated, and no serious adverse events were reported. (This study has been registered at ClinicalTrials.gov under registration no. NCT01202695.).
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Malkevich
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hopkins
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Bernton
authors.affiliation: Battelle Biomedical Research Center (BBRC), West Jefferson, Ohio, USA.
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: Meister
authors.affiliation: Battelle Biomedical Research Center (BBRC), West Jefferson, Ohio, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Vela
authors.affiliation: Worldwide Clinical Trials, San Antonio, Texas, USA.
authors.forename: George
authors.initials: G
authors.lastname: Atiee
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Johnson
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Nabors
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Aimes
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Ionin
authors.affiliation: Emergent BioSolutions, Gaithersburg, Maryland, USA skiadopoulosm@ebsi.com.
authors.forename: Mario H
authors.initials: MH
authors.lastname: Skiadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000276:immunology*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000097:blood; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy; D000080908:Broadly Neutralizing Antibodies; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D055815:Young Adult
chemical_list: C000601130:AVP-21D9; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D000080908:Broadly Neutralizing Antibodies
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