近日,新的吸入性炭疽治疗药物Anthim（obiltoxaximab）注射剂获美国（FDA）批准，这是一种单克隆抗体，旨在中和炭疽杆菌（anthrax）产生的毒素。Anthim由Elusys Therapeutics公司开发，通过FDA的动物法则（Animal Rule）获批用于吸入性炭疽的治疗及预防性治疗。 批准日期：2016年3月18日；公司：Elusys Therapeutics，Inc. ANTHIM®(obiltoxaximab)注射液，为静脉使用 美国初次批准：2016 作用机制 Obiltoxaximab是一个单克隆抗体结合炭疽杆菌的的保护性抗原(PA)[见微生物学]。 适应证和用途 ANTHIM®是一种直接针对炭疽杆菌的保护性抗原的单克隆抗体。它是适用在成年和儿童患者为由于炭疽杆菌吸入性炭疽病的治疗与适当抗菌药物联用和，为吸入性炭疽病当另外治疗是不能得到或是不适当的预防。 使用的限制 ANTHIM仅应当它对吸入性炭疽病的预防获益胜过超敏性和过敏性反应的风险时为预防使用。 ANTHIM的有效性是仅根据在吸入性炭疽病的动物模型中疗效研究。 在儿童人群中没有ANTHIM的安全性或药代动力学(PK)研究。在儿童患者利用群体PK方法衍生给药。 ANTHIM没有直接抗细菌活性。ANTHIM应与适当抗菌药物联用。 预期ANTHIM不跨越血脑屏障和不预防或治疗脑膜炎。 剂量和给药方法 预先给药用苯海拉明[diphenhydramine]。 ● ANTHIM的推荐剂量： 成年患者：16mg/kg。 儿童患者： 大于40kg：16mg/kg 大于15kg至40kg：24mg/kg 低于或等于15kg：32mg/kg ●作为一个历时1小时和30分钟静脉(IV)输注前在0.9%氯化钠注射液，USP稀释注射液。 在一个监视具备处理过敏性反应情况给予ANTHIM。 见完整处方资料对ANTHIM注射液的制备，稀释和给药指导。 剂型和规格 注射液：600mg/6mL(100mg/mL)溶液在单剂量小瓶中。 禁忌证 无 警告和注意事项 超敏性反应，包括过敏性反应(黑框警告) 不良反应 在健康成年受试者最频繁报道的不良反应 (≥1.5%)为头痛，瘙痒，上呼吸道感染，咳嗽，血管穿刺部位瘀伤，输注部位肿胀，鼻塞，输注部位疼痛，荨麻疹和肢体中疼痛。 报告怀疑不良反应，联系Elusys Therapeutics公司电话1-844-808-0222或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。 在特殊人群中使用 儿童使用：在儿童人群没有ANTHIM安全性或PK的研究。 供应/贮存和处置 ANTHIM注射液是一种无菌，无防腐剂，清澈至乳白色，无色至淡黄色至浅黄褐色溶液可能含少许半透明-至-白色蛋白质颗粒在单剂量小瓶中含600mg/6mL(100mg/mL)和可得到以下包装规格； 纸箱：含一个(1)单-剂量小瓶的ANTHIM 600mg/6mL(NDC 69604-204-02)。 贮存在冰箱在2°C至8°C(36°F至46°F)在原始纸盒以避光保护。不要冻结。不要摇晃。 obiltoxaximab (Anthim) (ETI-204) Anthim (obiltoxaximab) Injection for the Treatment of Inhalational Anthrax, United States of America Anthim (obiltoxaximab) is an injectable drug developed by Elusys Therapeutics for the treatment of inhalational anthrax caused by bacillus anthracis. Elusys Therapeutics submitted the biological license application (BLA) for the drug to the US Food and Drug Administration (FDA) on 20 March 2015. The BLA was accepted by the FDA and the drug was granted orphan drug designation in the US. The US FDA approved Anthim (obiltoxaximab) on 21 March 2016 as a treatment for inhalational anthrax in adults and children in combination with antibacterial drugs. Anthrax causes and types Anthrax is a chronic bacterial infection caused by gram positive, rod-shaped bacteria known as bacillus anthracis, which usually affects domestic and wild animals. There are different types of the illness namely cutaneous, inhalational, gastrointestinal and injection. Inhalational anthrax is the deadliest form and usually occurs when a person inhales spores present in the air, entering the body and infecting the lungs. The symptoms usually associated with the disease are fever, chills, chest discomfort, shortness of breath, dizziness, cough, nausea, stomach pain, headache, sweats, extreme tiredness and body aches. Inhalation anthrax is often diagnosed by chest X-ray or CT scans in suspected patients. Anthim's mechanism of action Anthim (obiltoxaximab) is a high-affinity humanised and deimmunised monoclonal antibody that binds to the protective antigen component of anthrax toxin. Anthim's toxin neutralising activity helps in preventing the entry of anthrax toxins produced by bacillus anthracis into the susceptible cells. The pathogenicity of the bacteria depends upon the two types of toxins namely lethal toxins (LT) and edema toxin (ET). The drug prevents the toxins entry thereby avoiding the spreading of the toxin throughout the body. Clinical trials on obiltoxaximab The US FDA's approval of Anthim (obiltoxaximab) was based on the results obtained from three phase 3 clinical trials conducted to evaluate the safety and efficacy of the single intravenous dose (16mg/kg) of obiltoxaximab in healthy adult men and women aged above 18 years. The first clinical trial was double-blind, randomised, placebo-controlled study, which enrolled 280 healthy adult subjects to demonstrate the safety and tolerability of repeat IV administration of obiltoxaximab (16mg/kg). The subjects were randomised to receive obiltoxaxim (210) and placebo (70). The adverse events reported during the trail were mild to moderate, whereas the most frequently reported AEs in subjects randomised to obiltoxaximab were pruritus, headache, rash and urticaria. The second trial was a double-blind, randomised and placebo-controlled study, which enrolled 70 healthy volunteers to demonstrate the safety and tolerability of repeat IV administration of obiltoxaximab (16mg/kg). The subjects were classified into two treatment groups Group A (35 Subjects) and Group B (35 subjects). Group A received Obiltoxaximab on days 1 and 14 and placebo on days 120 of the study; Group B received Obiltoxaximab on day 1 and 120 and placebo on day 14 of the study. The most adverse events reported during the study were infusion site swelling, erythema and pain. The third trial was an open-label, randomised, parallel group drug-drug interaction study to evaluate the safety and efficacy of obiltoxaximab when given along with ciprofloxacin. The study enrolled 40 healthy volunteers between 18 to 65 years. The subjects were placed into two treatment groups of 20 each. Group 1 received Obiltoxaximab (16mg/kg) and single dose IV ciprofloxacin (400mg) followed by an oral ciprofloxacin (750mg), whereas Group 2 received IV obiltoxaximab (16mg/kg) alone. The only adverse event reported during the trial was urticaria.