PRODUCT PIPELINE
ANTHIM™ ANTHRAX ANTI-TOXIN
Indication
Anthim is a very high-affinity 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 a human safety study.
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 dose provides complete protection
- A single intramuscular (IM) or intravenous (IV) dose with or without antibiotic, administered 6-12 hours post-exposure, was 100% protective in rabbits as a stand alone therapy, while survival with antibiotics alone was only 33%.
- A single IV dose demonstrated significant protection up to 48 hours after a lethal anthrax spore challenge
- Effective low dose allows for single dose IM delivery
Safety and PK
- Safe and well-tolerated when given to normal healthy human subjects at the anticipated therapeutic dose
- Co-administration with ciprofloxacin in human subjects is safe and well-tolerated and there is no pharmacokinetic interaction between the two drugs
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 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 IM delivery using pre-filled syringes or auto-injectors. Although an IV dosage form will also be available, IM delivery is considered 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. An Emergency Use Authorization application was filed on October 5, 2005, and supplemental information was submitted to that application in August, 2006.
Anthim was awarded NIAID Challenge Grants AI062546-01 and AI067185-01 for advanced development, including IM formulation and safety and efficacy studies. The Company has held meetings with the FDA, Biomedical Advanced Research and Development Authority (BARDA) and other government agencies to provide updates and to solicit guidance for continued development.
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