Regulatory Decision Summary for BioThrax
Review decision
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.
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What was the purpose of this submission?
The purpose of this extraordinary use Supplemental New Drug Submission (EUSNDS) submission is to seek marketing authorization of BioThrax for the post-exposure prophylaxis indication, when administered in conjunction with recommended antibacterial drugs.
Why was the decision issued?
Two doses of BioThrax administered post-challenge increased survival rates in rabbits who received BioThrax plus antibiotic therapy compared to those receiving antibiotic alone. This result demonstrated the additional benefit of post-exposure vaccination with BioThrax over antibiotic therapy alone.
Two pre-exposure animal studies showed a correlation between the vaccination-induced prior-to challenge toxin-neutralizing antibody (TNA) levels and the probability of survival following the challenge. A prior-to-challenge TNA NF50 (50% neutralization factor) level of 0.56 corresponds to a 70% probability of survival in rabbits; and TNA NF50 level 0.29 corresponds to a 70% probability of survival in monkeys.
Two clinical studies showed that after three doses of BioThrax, the antibody response in human reached a peak at Day 42 (2 weeks after the 3rd dose) and all subjects had seroconverted (≥4 times increase in antibody titer). On day 63, the TNA NF50 geometric mean titres (GMT) was 0.97 - 0.86, and 100% - 98.9% of subjects had at least a four-fold increase in TNA titer. In addition, on Day 63, 71.2% of subjects in one study achieved a TNA NF50 value ≥0.56. The results from both studies suggested that subjects develop a robust immune response after three subcutaneous doses of BioThrax at Week 0, 2, and 4, which supports the additional benefit of BioThrax to antibiotic treatment for post-exposure prophylaxis.
In another clinical study, the interference of BioThrax on the pharmacokinetic of ciprofloxacin was not observed, and adverse effects of ciprofloxacin on the immunogenicity of BioThrax were also not observed.
The safety profile was generally in line with previous studies that were discussed in the original EU NDS submission. The safety profile for BioThrax with ciprofloxacin was similar to that of BioThrax alone. No new safety concerns were identified.
In addition, the Centers for Disease Control and Prevention (CDC)s Anthrax Vaccine and Antimicrobial Availability Program provides supportive information in terms of safety of administration of 3-dose BioThrax with antibiotics. Based on the submitted non-clinical and clinical data, the benefits of BioThrax administered post exposure outweigh the risks with the proposed dose schedule (three subcutaneous doses at Week 0, 2, and 4).
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.