PRODUCTS
ANTHIM® ANTHRAX ANTI-TOXIN
Indication
Anthim is a very high-affinity humanized deimmunized monoclonal antibody, targeting anthrax toxin Protective Antigen, that has demonstrated significant efficacy against anthrax infection in lethal animal spore challenge studies. Further, Anthim was demonstrated to be safe and well-tolerated when administered with and without antibiotics in two human safety studies.
The indications for Anthim are pre-exposure and post-exposure prophylaxis of inhalational anthrax disease, as well as active treatment of disease both as a stand-alone therapy and in conjunction with antibiotics. The distinguishing features of Anthim are:
Efficacy (inhalation spore challenge):
- A single pre-exposure or early post-exposure dose provides complete protection from death
- A single intramuscular (IM) or intravenous (IV) dose with or without antibiotic, administered 6-12 hours post-exposure, was 100% protective in rabbits while survival with antibiotics alone was only 33%
- A single IV dose demonstrated 78% protection up to 54 hours after a lethal anthrax spore challenge in monkeys
- Effective low dose allows for rapid IM delivery
Safety and PK
- Well-tolerated in three clinical safety studies
- Co-administration with ciprofloxacin in human subjects was well tolerated at doses tested to date
Manufacturing and Formulation
- Established, large manufacturing partner for commercial production
- High production cell line utilizing established production technology
- Highly concentrated formulation allows for rapid intramuscular delivery
Mechanism of Action and Dosing
Anthim is highly effective because it completely neutralizes anthrax toxin before the toxin interacts with target cells. This high potency is due in part to the “affinity-enhancement” process carried out on a segment of the antibody binding region by the laboratories of Drs. George Georgiou and Brent Iverson at the University of Texas, Austin.1
Toxins function as virulence factors by essentially paralyzing immune system cells, allowing the spores and bacteria to evade clearance by phagocytosis. Efficacy studies have shown that Anthim prevents the spread of bacteria to the blood and to other organs and reduces the bacterial load in the lungs and lung associated lymph nodes. Anthim is being developed for both IV and IM administration. IM delivery provided emergency responders an essential method of drug delivery to treat large numbers of civilians in an emergency situation.
Development Status
An IND was filed on February 24, 2005, and Anthim has received Fast-Track and Orphan Drug status at FDA. The first in human safety study was completed in April, 2006, demonstrating a favorable safety profile and the data was presented at the 2006 ICAAC meeting. A second safety study at higher doses has been completed and a similar favorable safety profile was observed. In multiple efficacy studies conducted in two animal species, Anthim has shown the highest observed efficacy of an anti-toxin in studies of both prophylaxis and treatment of anthrax disease.
Government Support
Elusys maintains active communication with multiple branches of US government including HHS, FDA and DoD regarding the development of Anthim. Elusys has been awarded multiple grants and contracts in the past 8 years to support Anthim's continued development.
Most recently, Elusys was awarded a 5 year development contract for up to $143 Million of funding to complete the non-clinical, clinical, and commercial manufacturing development needed for procurement into the Strategic National Stockpile and FDA licensure under a BLA.
1. Maynard J, Maasen CB, Leppla SH, Brasky K, Patterson JL, Iverson BL, Georgiou G (2002) Protection
against anthrax toxin by recombinant antibody fragments correlates with antigen affinity. Nature Biotechnology 20(6):597-601