Regulatory Decision Summary for BioThrax
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
This submission was accepted as an extraordinary use new drug submission (EUNDS), under the Health Canada EUND pathway. It is not ethical to intentionally expose humans to a deadly bacterium and not feasible to conduct well-controlled clinical trials due to the rare occurrence and sporadic nature of cases of natural exposure, and the emergency use is in settings that require rapid intervention and at locations that cannot be predetermined. Therefore, the effectiveness of BioThrax is based on efficacy studies demonstrating a survival benefit in animal study.
The purpose of this extraordinary use new drug submission is to seek marketing authorization of BioThrax for the following proposed indication:
- BioThrax (Anthrax Vaccine Adsorbed, AVA) is indicated for active immunization for the prevention of disease caused by Bacillus anthracis, in individuals 18 through 65 years of age, whose occupation or other activities place them at risk of exposure, regardless of the route of exposure.
Why was the decision issued?
The primary assessment of the efficacy of BioThrax is the Brachman study, which was conducted in the 1950s with a BioThrax predecessor vaccine. This study demonstrated that the vaccine can provide protection to persons at occupational risk of exposure to B. anthracis spores. Additional supportive efficacy comes from a CDC Observational Study, using surveillance data from 1962-1974 and involving both BioThrax as well as the predecessor vaccine.
In 2005, the United States Food and Drug Administration (FDA) completed a comprehensive review of animal and human study data concerning different versions of the vaccine, and concluded that the predecessor vaccine (used in the Brachman study) and BioThrax "are comparable in their ability to protect test animals against challenge with virulent strains of B. anthracis and to elicit similar immune responses in humans".
As originally licensed, BioThrax and the predecessor vaccine were administered as a series of 6 subcutaneous (SC) priming doses over 18 months (0, 2, 4 weeks, and 6, 12, 18 months), followed by annual booster doses. A study, BB-IND 10031, was then conducted to find an optimized dosing schedule for BioThrax that included reducing the number of doses in the primary series as well as the route to intramuscular. The results showed that the anti-PA IgG responses induced by intramuscular route of administration were not lower, compared to subcutaneous route of administration. And while immune responses for the reduced 4 dose group evaluated at month 13, 19, and 31 declined significantly compared to the other groups, a booster dose (3 years after the primary doses) could elicit high titers of anti-PA IgG, which were not lower, compared to other dose schedules.
Administration of BioThrax subcutaneously or intramuscularly was generally tolerated however intramuscular administration elicited fewer injection site adverse events.
It was noted in Study BB-IND 10031 that for earlier protection at week 8, the dose schedule of week 0-2-4 was much better than a 3 dose schedule of week 0-4, in terms of anti-PA IgG level. Therefore, for the non-emergency situation, the week-2 dose can be omitted and a schedule of week 0-4 is considered sufficient. However, if a speedier robust protection is required, the week-2 dose should be given.
The results of a non-human primate (NHPs) study showed that the 3-dose (0, 1, and 6 months) IM priming series provided efficacy for up to 4 years in rhesus macaques, which showed that the subjects will be protected against anthrax disease during the time period between the 3-dose primary series (at month 6) and the 3-yearly booster (at month 42).
Based on the submitted non-clinical and clinical data, the benefits of BioThrax outweigh the risks with the proposed dose schedule (3-dose primary series followed by every 3 years booster dose).
For more information on Health Canadas decision, please view the Summary Basis of Decision.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.