BioDrugs. 2003;17(4):296-8. doi: 10.2165/00063030-200317040-00010.
PolyHeme is a chemically modified haemoglobin solution derived from human blood. It has been developed by Northfield Laboratories as an alternative to transfused blood for the treatment of acute blood loss (such as in trauma or surgery). Single molecules of haemoglobin are toxic to the kidneys and cause vasoconstriction. The haemoglobin molecules in PolyHeme are polymerised to create small chains of linked tetramers. In August 2001, Northfield Laboratories stated that it had submitted a Biologics Licence Application (BLA) to the US FDA for approval of PolyHeme as a blood substitute for use in the treatment of urgent, life-threatening blood loss. There were some undisclosed problems with the BLA, and the US FDA asked for more information before it would accept the application or allow the company to conduct a trial for this indication. In March 2003, Northfield Laboratories announced that it had received clearance from the US FDA to proceed with a pivotal phase III trial evaluating the safety and efficacy of PolyHeme in improving patient survival when used to treat severely injured and bleeding trauma patients at the scene of injury and during ambulance transport to the hospital. Because of the severity of patients' injuries, this trial will be conducted under federal regulations that allow clinical research in emergency settings without obtaining informed consent. This trial will be conducted in urban settings where transit times to hospital may be short and not long enough to demonstrate superiority to the control group, therefore dual primary endpoints of superiority and non-inferiority will be evaluated. Northfield Laboratories has initiated a public disclosure and community consultation process; because informed consent will not be possible, this is one of the US FDA requirements that must be met prior to initiating the trial. In June 2003, Northfield Laboratories reached an agreement with the US FDA on Special Protocol Assessment (SPA) for the trial. The SPA is an acknowledgment and agreement between the trial sponsor and the US FDA for successful completion of the proposed trial to form the primary basis for an efficacy claim. In October 2002, Northfield Laboratories announced that it was collaborating with the US Army in developing a treatment Investigational New Drug Application (IND) for the battlefield use of PolyHeme. The IND is being developed to gain authorisation for the use of PolyHeme in patients in shock in remote battlefield settings, where red blood cells are not available. Phase III trials in the UK, Germany and Sweden are underway with Pharmacia Corporation (now Pfizer), who has licenced PolyHeme in these countries. On 16 April 2003, Pharmacia Corporation was acquired by, and merged into, Pfizer. Northfield Laboratories' US phase III trials have focused on elective surgery indications while the European trials are focusing on surgery with acute trauma patients where large amounts of blood are lost. Up to 20 units of PolyHeme have been infused in US trials in trauma patients. This volume represents 200% of an average person's blood volume. Northfield Laboratories has estimated that of the approximately 14 million units of blood which were used for transfusions in the US in 2001, about 8.5 million units were for acute blood loss, for which patient charges amounted to an estimated $US2.5 billion. The US transfusion market consists of two principal segments: the acute blood loss segment, which accounts for about 60% of the total market according to Northfield Laboratories, and the chronic blood loss segment, accounting for the remaining 40%. The former includes transfusions in connection with trauma, surgery and unexpected blood loss, while the latter includes transfusions used in general medical applications and chronic anaemias. Northfield Laboratories believes that PolyHeme's largest potential is in the elective surgery market, at the time estimated to use approximately 6.5 million units of blood in the US annually.Earlier, on 7 March 2003, the newswires quoted er, on 7 March 2003, the newswires quoted the CEO of Northfield Laboratories, stating that it is to administer 10 000 units of PolyHeme to 20 US trauma centres, following US FDA approval of a third phase III trial. Pending market approval of PolyHeme, the company will initially produce 75 000 units of the product, but expects this to increase to 400 000 units annually. Wall Street analysts have estimated the market potential for a substitute blood product to be in the "multibillion-dollar" range, according to the CEO. However, launch of PolyHeme was at the time said to be "a couple of years away".
聚血宝（PolyHeme）是一种源自人血的化学修饰血红蛋白溶液。它由诺斯菲尔德实验室（Northfield Laboratories）研发，作为输血的替代品用于治疗急性失血（如创伤或手术中出现的失血情况）。单个血红蛋白分子对肾脏有毒性并会导致血管收缩。聚血宝中的血红蛋白分子聚合形成连接的四聚体小链。2001年8月，诺斯菲尔德实验室称已向美国食品药品监督管理局（US FDA）提交生物制品许可申请（BLA），以批准聚血宝作为血液替代品用于治疗紧急、危及生命的失血情况。该BLA存在一些未披露的问题，美国食品药品监督管理局要求提供更多信息后才会接受该申请或允许公司开展针对此适应症的试验。2003年3月，诺斯菲尔德实验室宣布已获得美国食品药品监督管理局的批准，可进行一项关键的III期试验，评估聚血宝用于治疗严重受伤且出血的创伤患者在受伤现场及救护车转运至医院期间提高患者生存率的安全性和有效性。由于患者伤势严重，该试验将依据联邦法规进行，允许在紧急情况下进行临床研究而无需获得知情同意。该试验将在城市环境中进行，那里到医院的转运时间可能较短且不足以证明优于对照组，因此将评估优越性和非劣效性这两个主要终点。诺斯菲尔德实验室已启动公众披露和社区咨询程序；由于无法获得知情同意，这是美国食品药品监督管理局在启动试验前要求必须满足的条件之一。2003年6月，诺斯菲尔德实验室与美国食品药品监督管理局就该试验的特殊方案评估（SPA）达成协议。SPA是试验申办方与美国食品药品监督管理局之间的一份认可和协议，旨在成功完成拟议试验，以此作为疗效声明的主要依据。2002年10月，诺斯菲尔德实验室宣布正在与美国陆军合作，为聚血宝在战场上的使用开发一种治疗性研究新药申请（IND）。该IND正在开发中，以便获得在偏远战场环境中休克患者使用聚血宝的授权，因为在那里无法获得红细胞。在英国、德国和瑞典，与辉瑞公司（Pfizer，辉瑞公司收购了原法玛西亚公司（Pharmacia Corporation），法玛西亚公司已在这些国家获得聚血宝的许可）合作的III期试验正在进行。2003年4月16日，法玛西亚公司被辉瑞公司收购并合并。诺斯菲尔德实验室在美国的III期试验聚焦于择期手术适应症，而欧洲的试验则聚焦于有大量失血的急性创伤患者的手术。在美国针对创伤患者的试验中，已输注多达20单位的聚血宝。这个量相当于一个普通人血液量的200%。诺斯菲尔德实验室估计，2001年美国用于输血的约1400万单位血液中，约850万单位用于急性失血，患者为此支付的费用估计达25亿美元。美国输血市场主要由两个部分组成：急性失血部分，据诺斯菲尔德实验室称，约占总市场的60%；慢性失血部分，占其余的40%。前者包括与创伤、手术和意外失血相关的输血，而后者包括一般医疗应用和慢性贫血中使用的输血。诺斯菲尔德实验室认为聚血宝最大的潜力在于择期手术市场，当时估计美国每年在该市场使用约650万单位血液。早些时候，2003年3月7日，新闻通讯社援引诺斯菲尔德实验室首席执行官的话说，在美国食品药品监督管理局批准一项III期试验后，将向美国二十个创伤中心施用10000单位的聚血宝。在聚血宝获得市场批准之前，该公司最初将生产75000单位的产品，但预计年产量将增至400000单位。据首席执行官称，华尔街分析师估计替代血液产品的市场潜力在“数十亿美元”范围内。然而，当时称聚血宝的推出“还需几年时间”。
