AVANIR Anthrax Antibody Effective at Neutralizing Key Anthrax Toxin in Live Animal Model

SAN DIEGO -- AVANIR Pharmaceuticals presented in vivo animal data on its fully human antibody against the key toxin of the Class A biowarfare agent anthrax at a national symposium in Maryland today. The data showed that one molecule of the antibody, AVP-8C1, is capable of neutralizing more than two anthrax toxin molecules in rat models. This ratio shows exceptional potency and is the first example of an antibody's potency against a toxin at this very high or "sub-stoichiometric" level.

The presentation, "Anthrax Vaccination: A Source for a Panel of Potent Fully Human Monoclonal Antibodies using Xenerex Technology" was given at the 9th National Symposium -- Basic Aspects of Vaccines by Dr. Phillip Morrow, a co-inventor of AVANIR's Xenerex technology. Through the use of its Xenerex technology, AVANIR has discovered and developed a human monoclonal antibody that provides immediate post-exposure neutralization and immediate immunity in rats exposed to a lethal dose of recombinant anthrax toxins.

The antibody, AVP-8C1, binds to and neutralizes the protective antigen (PA). PA is a component of the anthrax toxins that plays a pivotal role in providing a portal for lethal factor (LF) and edema factor (EF) to enter the intracellular compartment and have a lethal effect. AVANIR's preclinical research to date demonstrates that a single dose of AVP-8C1 completely protects rats subsequently exposed to a lethal dose of recombinant anthrax toxins.

"The potency this antibody exhibits is extremely high," said Morrow. "We are very encouraged by this data, and plan to develop this antibody for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Although speculative, AVP-8C1 may also play a role in the prevention and treatment of infections by antibiotic-resistant strains of anthrax."

"The data from this antibody demonstrates that our Xenerex technology, a proprietary technology developed by AVANIR, is well suited to generating human antibodies that may be useful for the treatment of important infectious diseases," said Gerald J. Yakatan, President and CEO of AVANIR Pharmaceuticals. "And because of the relative potency of antibodies such as AVP-8C1, significant advantages in the cost of producing the product are possible."

AVANIR Pharmaceuticals is developing AVP-8C1 for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Grants from the U.S. Department of Defense administered through CCAT -- Center for Commercialization of Advanced Technology -- have already been awarded to facilitate the company's early antibody development efforts. AVANIR plans to work with federal authorities and the federal grant programs available under recently implemented biodefense initiatives to fund the required testing and eventual production of an antibody product. AVANIR is also in discussions with potential partner companies capable of antibody production in an effort to file an Investigational New Drug application seeking to begin clinical trials to evaluate the safety, tolerability, and pharmacology of AVP-8C1 in healthy human subjects.

There are three types of anthrax exposure: cutaneous, gastrointestinal and inhalational, of which the latter form is the most lethal. Currently, two options are available for the prevention or treatment of anthrax exposure, a vaccine and antibiotics. Both approaches have limitations. The current anthrax vaccine may take several weeks following the first doses before immunity is established, and requires multiple injections over a period of eighteen months, in addition to annual boosters, to maintain its presumed protective effect. Antibiotics, the standard treatment of anthrax infection, are effective in killing anthrax bacteria, but have limited use once the anthrax toxins are released. The natural emergence or deliberate release of antibiotic-resistant strains of anthrax is an ongoing public concern.

In AVP-8C1, AVANIR Pharmaceuticals has exploited a third mechanism of defense against anthrax infections. In contrast to the anthrax vaccine, the protection afforded by a single dose of AVP-8C1 would be immediate. In contrast to antibiotics, AVP-8C1 acts against the key gateway component PA of the anthrax. By neutralizing this molecule the LF and EF toxins are denied entry into cells. AVP-8C1 can be envisaged in multiple scenarios, augmenting vaccination, as a stand-alone prophylaxis, or synergistic in combination with antibiotics. The discovery and development of antibodies to the toxins of anthrax can meet significant unmet medical needs by providing protection from exposure to anthrax as well as extending the treatment window for those who are infected with anthrax.

AVP-8C1 is currently in preclinical development for use as a prophylactic and therapeutic drug to prevent and treat anthrax infections. Under the Bioterrorism Act of 2002, the FDA gave guidance on the evidence required to demonstrate the efficacy of new drug and biological products used to counter biological agents, when traditional efficacy studies in humans are not feasible. According to the guidelines, successful studies in relevant animal models will be considered sufficient to establish efficacy for licensure and marketing approval. AVP-8C1 is effective in preventing the lethal effects of anthrax toxins in the rat model. AVP-8C1 will be further evaluated in rabbits and nonhuman primates using Bacillus anthracis spore challenge. According to the guidelines, human clinical trials will be required to establish safety, tolerability, and pharmacology, but not efficacy.

Source: AVANIR Pharmaceuticals

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