title: Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax.
abstract: The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery.
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Yamamoto
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Shadiack
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: Battelle, West Jefferson, Ohio, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sanford
authors.affiliation: Battelle, West Jefferson, Ohio, USA.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Henning
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Nestor
authors.initials: N
authors.lastname: Gonzales
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: O'Connor
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA.
authors.forename: Leslie S
authors.initials: LS
authors.lastname: Casey
authors.affiliation: Elusys Therapeutics, Inc., Pine Brook, New Jersey, USA nserbina@elusys.com.
authors.forename: Natalya V
authors.initials: NV
authors.lastname: Serbina
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000992:Antitoxins / Q000008:administration & dosage / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects / Q000472:pathogenicity*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D056990:Post-Exposure Prophylaxis; D065129:Pre-Exposure Prophylaxis; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D000992:Antitoxins; C000611266:obiltoxaximab