Emergent BioSolutions Canada (Previously Cangene Corporation), Winnipeg, MB, Canada.
Battelle Biomedical Research Center, Columbus, Ohio, United States of America.
PLoS One. 2023 Mar 17;18(3):e0283164. doi: 10.1371/journal.pone.0283164. eCollection 2023.
To meet the requirements of the Animal Rule, the efficacy of monotherapy with ANTHRASIL® (Anthrax Immune Globulin Intravenous (Human)) for inhalational anthrax was evaluated in blinded studies using rabbit and nonhuman primate models. Animals in both studies were randomized to treatment groups exposed to ~ 200 LD50 Bacillus anthracis (Ames strain) spores by the aerosol route to induce inhalational anthrax. Rabbits (N = 50/group) were treated with either 15 U/kg ANTHRASIL or a volume-matching dose of IGIV after disease onset as determined by the detection of bacterial toxin in the blood. At the end of the study, survival rates were 2% (1 of 48) in the IGIV control group, and 26% (13 of 50) in the ANTHRASIL-treated group (p = 0.0009). Similarly, ANTHRASIL was effective in cynomolgus monkeys (N = 16/group) when administered therapeutically after the onset of toxemia, with 6% survival in the IGIV control and a dose-related increase in survival of 36%, 43%, and 70% with 7.5, 15 or 30 U/kg doses of ANTHRASIL, respectively. These studies formed the basis for approval of ANTHRASIL by FDA under the Animal Rule.
为满足动物法则的要求,使用兔和非人灵长类动物模型的盲法研究评估了 ANTHRASIL®(炭疽免疫球蛋白静脉内(人用))单药治疗吸入性炭疽的疗效。两项研究中的动物均随机分为治疗组,通过气溶胶途径暴露于约 200LD50 炭疽芽孢杆菌(Ames 株)孢子以诱导吸入性炭疽。兔子(每组 50 只)在疾病发作后,即通过血液中细菌毒素的检测确定,用 15U/kg 的 ANTHRASIL 或等体积的 IGIV 治疗。研究结束时,IGIV 对照组的存活率为 2%(48 只中的 1 只),而 ANTHRASIL 治疗组的存活率为 26%(50 只中的 13 只)(p=0.0009)。同样,当在毒血症发作后进行治疗时,ANTHRASIL 对食蟹猴也有效,IGIV 对照组的存活率为 6%,而用 7.5、15 或 30U/kg 剂量的 ANTHRASIL 治疗时,存活率分别有 36%、43%和 70%的剂量相关性增加。这些研究为 FDA 根据动物法则批准 ANTHRASIL 提供了依据。