Dataset Information

Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.

ABSTRACT: Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks. Obiltoxaximab 16 mg/kg in humans provided exposure beyond that of 16 mg/kg in animals, ensuring a sufficient duration of PA neutralization to allow for adaptive immunity development. Our approach to dose translation may be applicable to other agents being developed under the Animal Rule.

SUBMITTER: Nagy CF

PROVIDER: S-EPMC5245108 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.

Nagy C F CF Mondick J J Serbina N N Casey L S LS Carpenter S E SE French J J Guttendorf R R

Clinical and translational science 20161207 1

Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 1 ...[more]

PMID: 27925405

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Project description:BackgroundIn Bangladesh, the zoonotic transmission of anthrax from animals to humans poses substantial challenges for prevention and control programs, especially in resource-constrained settings. A comprehensive literature review was conducted focusing on anthrax infections in animals, humans, and the environment to enable better design of prevention and control strategies.Materials and methodsWe followed PRISMA guidelines to collect data on anthrax infection in animals and humans from reports between 1980 and January 2023. We used a standardized data extraction template to collect data on study location, year, hosts, deaths and risk factors responsible for anthrax occurrences at the animal, human and environmental sectors. Subsequently, we conducted a thorough analysis of the data gathered to identify the factors responsible for anthrax occurrences and to propose updated strategies for anthrax prevention and control.ResultsOf the 27 articles analyzed, 20 focused on animal or human anthrax, while seven addressed environmental contaminations. A total of 6354 cases of anthrax infection in animals were recorded, with 998 fatalities and an overall case fatality of 15.7 %. In humans, inadequate knowledge about anthrax and its transmission was a significant factor. Risk factors for human cutaneous anthrax included activities such as slaughtering diseased animals and contact with contaminated raw meat or blood. Risky practices such as disposal of animal carcasses in floodwaters or water bodies were observed in some areas, contributing to the persistence of the anthrax pathogen in the environment.ConclusionsOur study highlights the necessity of a multisectoral One Health approach to effectively control and prevent anthrax outbreaks in both animals and humans. This approach should include comprehensive vaccination programs, social and behavioral change activities, environmental management, and the establishment of surveillance systems. Implementing these recommendations will be crucial in addressing the complex challenges posed by anthrax in low-resource settings.

Dataset Information

Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.

Publications

Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule.

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