Sep 05 2013
PINE BROOK, NJ AND VICTORIA, B.C., CANADA,—Elusys Therapeutics, Inc. (Elusys), a biopharmaceutical company developing antibody therapies to treat infectious disease, presented key findings from nonclinical studies evaluating the company’s anthrax anti-toxin therapy, ETI-204 (Anthim), at the International Conference on Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis (Bacillus ACT). ETI-204, an anthrax anti-toxin, is an investigational agent in late stage development for the treatment of inhalational anthrax infection. Bacillus ACT is taking place this week in Victoria, British Columbia, Canada.
The poster presentation, “Pharmacokinetics of ETI-204, An Anti-PA Monoclonal Antibody, In Healthy and Anthrax-Infected Rabbits and Monkeys Following IV and IM Administration,” discussed pharmacokinetic (PK) parameters of ETI-204 in healthy and anthrax-infected animals when administered either intravenously (IV) or via intramuscular injection (IM). In healthy animals, absolute bioavailability of IM ETI-204 was 100% (rabbits) and 73% (monkeys). PK of ETI-204 was also examined in animals following challenge with aerosolized B. anthracis spores. ETI-204 administration to infected animals via IV dosing at the first sign of infection or via IM dosing at pre-determined time points post-challenge showed similar exposures within a species over the first week. An increase in clearance of free ETI-204 in infected compared to uninfected animals was observed for both IV and IM routes of administration and for both animal species; however, the absolute bioavailability of IM ETI-204 in infected animals was similar to or better than in healthy animals (97% in rabbits and 84% in monkeys). Together with animal efficacy data and healthy human PK data, these analyses will be used to select a human dose for the management of inhalation anthrax.
Data from two animal studies evaluating ETI-204 in combination with levofloxacin (antibiotic therapy) were reviewed in a poster titled “Rabbit Model of Anthrax For Exploring Complementarity of Antitoxin/Antibiotic Combination Therapy on Survival and Development of Adaptive Immunity.” In a 72-hour post-challenge, delayed treatment study, rabbits received either a single IV dose of ETI-204 (16 mg/kg) administered in combination with 6.5 mg/kg/day of levofloxacin for 3 days, levofloxacin alone or control. Survival at day 28 for the combination arm, levofloxacin arm and control was 68%, 58% and 0% respectively. Antibiotic therapy alone significantly reduced bacteremia (evidence of bacteria in the blood stream) but did not rapidly reduce protective antigen (PA) in all animals. Co-administration of ETI-204 with antibiotic therapy led to a significant (p=0.0001) reduction in free PA in all animals by 24 hours after dosing and showed a trend toward improved survival rate (74% vs 61% with antibiotic therapy alone).
A second rabbit study was reported in which anthrax-infected animals were treated with either ETI-204 IV (16 mg/kg), levofloxacin (50 mg/kg/day x 3 days), the combination of ETI-204 plus levofloxacin, or control 30 hours after challenge with anthrax. Surviving animals from the treated groups along with a naïve age-matched control group were re-challenged with anthrax nine months later and the development of adaptive immunity was evaluated. Survival results for the re-challenge were 100%, 95%, 89% and 0% respectively. It was found that animals treated with ETI-204, levofloxacin, or a combination of the two after, being exposed to and surviving anthrax infection, developed their own neutralizing anti-anthrax antibodies that likely provided protection against a second anthrax exposure.
A third poster presentation, “Detection of Endogenous Anti-PA Antibodies in Anthrax-Infected Rabbits After Treatment with ETI-204 and Bacteremia’s Influence on Survival,” highlighted data demonstrating that treatment with ETI-204 alone showed a dose dependent increased survival rate in inhalation anthrax-infected rabbits, and that bacteremia levels at the time of dosing had a significant effect on the probability of survival. Animals were exposed to B. anthracis spores and treated with a single IV dose of ETI-204 (1, 4, 8 or 16 mg/kg) at the first sign of increased body temperature or circulating protective antigen (PA). All control animals succumbed to anthrax by Day 5 while ETI-204-treated animals showed a dose dependent increase in survival (17%, 33%, 69% and 63%, respectively). All survivors in the 16 mg/kg group developed detectable anti-PA antibodies by 10 days after dosing.
“We are very encouraged with the data presented this week demonstrating the ability of ETI-204 to improve survival in rabbits at multiple dose levels and suggesting the potential for ETI-204 to reduce toxemia resulting from challenge with B. anthracis infection,” said Elizabeth Posillico, PhD, President and Chief Executive Officer of Elusys. “ETI-204 is being evaluated in both IV and IM routes of administration, and continues to show promise for the treatment of inhalational anthrax infection.”
Anthrax is a life-threatening infectious disease caused by the bacterium Bacillus anthracis and remains one of the nation’s top biowarfare threats. Much of the morbidity and mortality of anthrax can be attributed to anthrax toxins. Inhaled anthrax is often fatal, despite treatment with antibiotics. In the 2001 anthrax letter attacks, inhalational anthrax had a fatality rate of approximately 50% in humans infected, even when victims were given antibiotics and supportive hospital care.
ETI-204 is formulated as a solution and is the only anthrax anti-toxin in advanced stages of development that is being investigated for both IV and IM administration. A product that can be given IM as well as IV is highly desirable because it could provide the capability to more rapidly administer product to people outside of a hospital setting or when IV administration is not feasible.
ETI-204 is a high-affinity, humanized and deimmunized monoclonal antibody that targets the protective antigen of B. anthracis and neutralizes the lethal effects of anthrax toxins by binding to Protective Antigen. It is an investigational agent being developed for treatment of inhalational anthrax. ETI-204 is formulated as a solution and is being evaluated for intravenous (IV) and/or intramuscular (IM) administration.
ETI-204 efficacy and safety is being studied in animal models of inhalational anthrax and safety studies are being conducted with human volunteers. Three studies assessing pharmacokinetics and safety of intravenous (IV) administration of ETI-204 in humans have been completed. The more common adverse events related to ETI-204 administration across the three studies included upper respiratory tract infection, nausea, headache, nasal congestion and erythema. ETI-204 was granted Fast Track status and Orphan Drug Designation by the FDA.
This program is supported with federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), the Department of Health and Human Services (HHS) under Contract Nos. HHSO100201000026C and HHS0100201100034C.
About Elusys Therapeutics, Inc.
Elusys Therapeutics, a private company based in Pine Brook, NJ, is focused on the development of antibody therapeutics for the treatment of infectious disease. Elusys has been engaged in the development of ETI-204, an anthrax biowarfare countermeasure since 2000. The company has received multiple grants and contracts totaling over $200 million to support the development of ETI-204 to protect people in the event of an anthrax attack. Today, ETI-204 has advanced to the final stages of development, and is closer to achieving the company’s goals of receiving FDA licensure and becoming part of the Strategic National Stockpile. For more information, please visit www.elusys.com.
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