Anthrax Immune Globulin to Prevent & Treat Anthrax: Advanced Product Development

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DESCRIPTION (provided by applicant): While antimicrobials are effective against the early stages of anthrax infection, delayed initiation of antimicrobial therapy or infection with an antibiotic resistant strain can produce a life-threatening toxemic state for which antimicrobials are not effective. In such cases, neutralization of the toxin is required because antimicrobials kill vegetative cells and have no effect on the toxin. Polyclonal antibodies to the B. anthracis exotoxin have the potential to immediately neutralize the toxin, providing a life-saving medical countermeasure and filling an important unmet need. The effectiveness of antibodies to the licensed vaccine BioThrax(r) or its major protein component, protective antigen (PA), to prevent and treat inhalational anthrax has been demonstrated in animal studies. In addition, human immune globulins have a long history of safety and success in treating infectious disease, and in particular, bacterial toxemia. Proposed herein is the advanced development of anthrax immune globulin for intravenous use (AIGIV). AIGIV is derived from Source Plasma from BioThrax-immunized donors and is produced using an FDA-approved immune globulin purification process. The use of a proven technology and a licensed manufacturing process provides a low- risk approach for the development of an effective, licensable antitoxin compared to other high-risk unproven technologies. EIS, through its sister company BioPort, has access to the only FDA-approved anthrax vaccine, and thus is in the unique position to generate the quantities of BioThrax Source Plasma necessary to produce AIGIV on a long-term basis. The AIGIV advanced development plan allows for release of a cGMP AIGIV lot by December 2006, which could make AIGIV doses available for use under Emergency Use Authorization within 18 months of award. The product would be indicated for treatment of inhalational anthrax due to antibiotic-susceptible or antibiotic-resistant B. anthracis in persons 18-65 years of age. An additional indication will be sought for the prophylaxis of inhalational anthrax for individuals at risk for having contact with, or who have contacted, either antibiotic-resistant or antibiotic-susceptible B. anthracis (pre-exposure and post-exposure prophylaxis). The Specific Aims for advanced development of AIGIV are to: 1) Conduct pharmacokinetic and tolerability studies, and pivotal Animal Rule efficacy studies in the rabbit and rhesus macaque models using cGMP AIGIV, and 2) Develop and validate anti-PA IgG and TNA assays to support manufacturing and for the measurement of AIGIV activity in animal sera. The initial cGMP lot of AIGIV will be used for Animal Rule studies to define the dose which provides prophylactic and therapeutic protection against aerosolized B. anthracis spore challenge.