The U.S. Food and Drug Administration’s (FDA) recent approval of a new indication for BioThrax came via the so-called Animal Rule.
A federal regulatory tool devised in 2002 following the 9/11 attacks, the Animal Rule allows animal efficacy data to be used as a basis for approval when human efficacy studies are not ethical or feasible, according to the FDA.
Nine other therapies to fight bacterial, chemical and radiological threats have been approved via the Animal Rule, but never a vaccine.
BioThrax is the first vaccine to receive approval based on the Animal Rule, according to Elizabeth Valenti, chair of the FDA review committee, in the summary basis for approval of the product’s increased indication.
“Clinical field trials to demonstrate effectiveness of an anthrax vaccine in a post-exposure setting are not feasible and human challenge studies are not ethical because of the rapid progression and fatal nature of the disease,” Valenti told Patient Daily. “Therefore, animal protection data was used as a basis for demonstration of effectiveness of the product for the proposed indication, per the Animal Rule.”
Specifically, the ability of BioThrax to increase the probability of survival after stopping post-exposure antibiotic treatment was assessed in rabbits, which were treated with both antibiotics and BioThrax. They had a survival rate of 70 percent to 100 percent, depending on the vaccine dose administered, according to the FDA.
In contrast, in two studies of rabbits that received only antibiotic treatment, survival rates were 44 percent and 23 percent, respectively.
Subsequently, the safety and antibody responses to BioThrax in humans were evaluated in a multi-center study conducted in the U.S. when under-the-skin injections were given to 200 healthy adults in three doses at zero, two and four weeks.
The FDA reported that the majority of study participants generated antibody responses that correlated to a 70 percent probability of survival that was observed in animal models.
The BioThrax vaccine -- used together with recommended antibiotic treatment -- will prevent anthrax disease following suspected or confirmed exposure to the bacterium that causes anthrax disease.
“While naturally occurring anthrax disease in humans is rare, the potential for use of Bacillus anthracis as a bioweapon has significantly increased the level of concern about the disease,” Valenti told Patient Daily. “Anthrax is one of the most feared of all bioweapons, primarily because the spores are very stable and very easy to disperse. The disease, especially the inhalation form of the disease, is often fatal if not promptly treated.”
Additionally, Valenti said, the new BioThrax post-exposure prophylaxis (PEP) immunization likely protects against disease resulting from residual spores that remain after completion of the recommended course of antibacterial drugs.
“Furthermore, addition of BioThrax to antibiotics for PEP may provide substantial benefit in preventing anthrax disease for individuals where poor compliance with antimicrobial therapy is documented,” she said.
Valenti added that the FDA found that data provided by BioThrax manufacturer Emergent BioDefense Operations Lansing LLC “demonstrated the benefit of BioThrax in [PEP] of disease following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with recommended antibacterial drugs,” namely the antibiotic Ciprofloxacin.
Initial U.S. approval for BioThrax -- Anthrax Vaccine Adsorbed -- occurred in 1970. Prior to the FDA’s recent increased indication for the vaccine’s use, BioThrax was indicated for the active immunization for the prevention of anthrax disease in persons 18 through 65 years of age for pre-exposure prophylaxis of disease in persons at high risk of exposure.