Human haemoglobin - Northfield.

Abstract

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".