By: Alex Chu, Staff Writer
On March 21 2016, the Food and Drug Administration (FDA) approved obiltoxaximab (Anthim®), an intravenous injection, for the treatment and prevention of inhalational anthrax toxicity for adult and pediatric patients. Developed by Elusys Therapeutics, obiltoxaximab is a monoclonal antibody that binds to the protective antigen of anthrax, which is a cell binding protein component of anthrax toxin.1,4,5 The cell binding protein components of obiltoxaximab are composed of edema factor and lethal anthrax factor, which are thought to be the enzymatic toxins responsible for its pathology. Obiltoxaximab inhibits the entry of lethal anthrax and edema factors into cells.1,4,5
Although cases of anthrax are rare in the U.S., it is a life-threatening, infectious disease with a fatality rate of 45% if left untreated.2 Due to its lethality and ease of intentional transmission through the air, the CDC (Centers for Disease Control) notes that anthrax is regarded as a biological warfare and bioterrorism threat listed under Category A, and therefore poses the highest risk to national security and health.2 Because treatment for anthrax is critical in maintaining health and combating bioterrorism, obiltoxaximab was approved under the FDA Animal Rule. Under this rule, findings from adequate and well-controlled animal studies that demonstrate drug efficacy may be used in obtaining drug approval in situations where it is normally unfeasible, such as conducting clinical trials in humans with anthrax due to its high fatality rate.1,4,5
The efficacy of obiltoxaximab was demonstrated in four double-blinded clinical studies involving NZW rabbits and cynomolgus macaques. In the trial, the animals were given aerosolized B. anthracis spores at doses much higher than lethal doses in order to achieve a mortality rate of 100% , if left untreated.1 Treatments of either obiltoxaximab or placebo were administered after positive serum electrochemiluminescence assay levels which indicate infection, were detected in the blood.1 The animals were observed for survival 28 days after initial administration of the spores.1 In studies 1 and 2 that involved NZW rabbits, none of the rabbits that were administered placebo (n=9, n=13) survived in comparison to the 93% and 62% that survived after obiltoxaximab was administered (n=14/p=0.0010, n=13/p= 0.0013).1 In studies 3 and 4, 6% and 0% of cynomolgus macaques survived after administration of placebo (n=16, n=17) as compared with 47% and 67% with obiltoxaximab ( n=15/p=0.068, n=33/p=0.0055).1
The safety of obiltoxaximab was studied in 320 healthy subjects over the course of three clinical trials.1,3 Study 1 was a placebo-controlled study evaluating adverse reactions between a single dose of 16mg/kg IV obiltoxaximab vs placebo (n=210, n=70 ).1 Study 2 was a repeat dose study in which 70 subjects received one dose, and then 34 and 31 subjects received a second dose 2 weeks and 4 months apart, respectively.1 Study 3 was a drug interaction analysis of 40 subjects in which half of the subjects received a single dose of obiltoxaximab while the other half received obiltoxaximab plus ciprofloxacin for 9 days.1 The combined results from studies 1 and 2 demonstrate that the most common adverse reactions resulting from administration of single dose obiltoxaximab vs placebo (n=300, n=70) were headaches (8% vs 6%), itching (4% vs 1%), and upper respiratory tract infections (5% vs 3%)1 Overall, patients who were pre-medicated with diphenhydramine were found to be less likely to experience adverse reactions compared to those who were not (42% vs 58%).1 Findings of the drug interaction analysis indicate that co-administration of ciprofloxacin orally or intravenously, did not alter pharmacokinetic properties of obiltoxaximab and resulted in higher survival outcomes than antibacterial therapy alone.1,4
Because of how rare and deadly anthrax is, obiltoxaximab is mainly used by militaries and federal agencies such as the CDC (Centers for Disease Control) and the National Institute of Health for emergency preparation and public health. The recent approval of obiltoxaximab adds an additional treatment and prevention option for anthrax toxicity as opposed to treatment with antibiotics.
- Anthim (Obiltoxaximab) [package insert]. Pine Brook,NJ; Elusys Therapeutics; Revised 3/01/2016. Accessed 4/27/2016.
- Centers for Disease Control and Prevention. Anthrax 2009. Available at: http://www.cdc.gov/nczved/divisions/dfbmd/diseases/anthrax/technical.html. Accessed 4/27/2016.
- U.S. Food and Drug Administration. Drug trials snapshot: ANTHIM 2016. Available at: http://www.fda.gov/drugs/informationondrugs/ucm494083.htm#collapsefive. Accessed 4/27/2016.
- Press Releases. Elusys therapeutics receives FDA approval for ANTHIM® (obiltoxaximab) injection 2016. Available at: http://www.prnewswire.com/news-releases/elusys-therapeutics-receives-fda-approval-for-anthim-obiltoxaximab-injection-for-the-treatment-and-prophylaxis-of-inhalational-anthrax-300238750.html. Accessed 4/27/2016.
- U.S. Food and Drug Administration. FDA approves new treatment for inhalation anthrax 2016. Available at: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm491470.html. Accessed 4/27/2016.