Posted: June 17, 2002
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PART II
Several oxygen therapeutic products currently are in late-stage clinical trials. In preparation for the emergence of this totally new class of oxygen delivery agents, AABB held an Oxygen Therapeutics and Transfusion Alternatives Conference from May 30 to 31. The following is Part II in a series that provides highlights from conference presentations and discussions. For Part I in the series, see the June 7 issue of AABB Weekly Report.
Information was presented at the conference on three oxygen therapeutic products currently in clinical trials. Alliance Pharmaceutical Corp.'s perflubron emulsion product, Oxygent©, has a shelf life up to two years, according to Pieter Keipert, PhD, director of the company's Oxygen Carriers Development program.
In European Phase II trials, Oxygent© was able to reduce hemoglobin-based transfusion triggers, thereby delaying the need for blood transfusion", Keipert said. In the control group studied in these trials, patients whose hemoglobin dropped below 8 g/dl. required transfusion, while the patient group that had been treated with Oxygent© did not need transfusion until their hemoglobin dropped below 6 g/dl.
Phase III surgery trials, to date, have achieved "a significant reduction and avoidance of blood transfusion, with the benefit maintained through hospital discharge", Keipert said. Surgery patients treated with Oxygent© also needed fewer units of allogeneic blood than control groups. Alliance's Phase III coronary artery bypass grafting (CABG) studies were temporarily halted after some patients experienced stroke. However, there is "no direct evidence that the drug itself is implicated in these adverse events", Keipert said.
Hemosol Corp.'s hemoglobin raffimer product, Hemolink©, is derived from outdated blood products. In Phase III trials in Canada and the United Kingdom, Hemolink© has been shown to reduce the rate of allogeneic blood transfusions given to patients undergoing CABG surgery.
"Our strategy has been to dose and re-dose patients with Hemolink© to maintain a certain oxygen level and to keep oxygenation going for days or even weeks", explained Lou Carmichael, MD, PhD, medical director at Hemosol.
One clinical trial involved 299 patients undergoing CABG in conjunction with a blood conservation technique called intra-operative autologous donation (IAD). IAD is a technique in which the patient's own blood is withdrawn just prior to surgery. Following administration of Hemolink©, the patient's own fresh blood is re-administered over the course of the procedure as needed. Up to five days after surgery, 22 percent of patients treated with Hemolink© had received RBC transfusions, while 27 percent of patients in the control group had been transfused.
On June 7, Hemosol announced delays in the reporting of data from its other Phase III clinical trials in Canada and the U.K.
According to the company, a CABG study involving patients undergoing a repeat or "re-do" procedure has been slowed by the "significant competing demands" of another CABG trial.
"The company does not expect to report data from this trial in the third quarter of this year as originally planned", Hemosol announced. "As enrollment progresses, an update on both trials will be provided when the company releases its second quarter results.
The timing of the response to the [U.K.'s] Medicines Control Agency (MCA), regarding the company's pending application to market Hemolink© in the U.K. will be dependent on the availability of data from these ongoing studies."
Northfield Laboratories' human polymerized hemoglobin product, PolyHeme©, also made from outdated blood products, has a shelf life greater than one year, according to Stephen Gould, MD, president of the company. One unit of PolyHeme contains 50 grams of modified hemoglobin, approximately the same amount of hemoglobin delivered by one unit of transfused blood. "We believe it is appropriate to say hemoglobins are interchangeable", Gould said.
In human clinical trials, PolyHeme© has been shown to be a safe and effective alternative to Red Blood Cell transfusion. In one study, 44 trauma patients were randomized to receive either RBCs or up to 300 g of PolyHeme©. At one day out from surgery, the control group had received a total of 10.4 units of RBCs, while the group treated with PolyHeme© received a total of 6.8 units. At three days from surgery, these numbers were 11.3 and 7.8, respectively.
Gould said results from the product's Phase III trials will be published in the July issue of Transfusion.
Military Uses for Oxygen Therapeutics
"Does the U.S. military need an oxygen therapeutic?" asked Col. G. Michael Fitzpatrick, PhD, MT(ASCP)SBB, director of the Armed Services Blood Program (ASBP). "The short answer is Yes." Fitzpatrick explained that because ASBP is responsible for shipping blood products to troops around the world, time considerations are different for his program than for civilian blood programs. From the time that ASBP is notified of a need for blood in a particular region, it can take anywhere from four to 10 days for the necessary units to be retrieved, loaded onto an airplane, and shipped to the area in need. "By the time the blood arrives, its shelf life already has been significantly reduced", Fitzpatrick said.
ASBP's frozen blood program maintains adequate supplies of frozen blood to cover the intervening four to ten days, with 60,000 units of O+ and O- blood strategically prepositioned around the world. However, frozen blood units must be replaced every five to 10 years to keep up with new infectious disease testing, and the cost of the program is mounting. In 2002, the U.S. armed services spent U.S.$1 million on modernizing the frozen blood program, and the cost is expected to increase to U.S.$4.6 million in 2003.
Oxygen therapeutics could complement ASBP's frozen blood program by providing transfusion alternatives in a variety of military situations, Fitzpatrick said. "It only makes sense to develop a blood inventory management system and 'new' products that provide a constant safe and adequate blood supply to alleviate shortages that now regularly occur and undermine the public's confidence."
Part I