By Kim Coghill
For the second time this year, Alliance Pharmaceutical Corp.'s stock climbed following the release of promising results from clinical trials of Oxygent, an intravascular oxygen carrier.
The company is testing Oxygent for both general surgery and cardiac patients. San Diego-based Alliance said Monday that a Phase III international study of 492 general surgery patients shows that the average number of units of blood required by the control patients was twice the number of units required by patients treated with Oxygent (perflubron emulsion). The data were presented at the European Society of Anesthesiology Annual Meeting in Gothenburg, Sweden, by Donat Spahn, Alliance's lead investigator, and professor and chairman of the Department of Anesthesiology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Alliance's stock (NASDAQ:ALLP) gained 32.5 percent Monday, or 86 cents, to close at $3.48.
In mid-March, the company's stock shot up 58 percent after it released preliminary data showing that there was no evidence to link Oxygent to certain adverse events in cardiac patients. Instead, it was determined that the design of the cardiac trial, not the drug, likely was the culprit. Two months prior, Alliance was forced to suspend enrollment of the Phase III cardiac study due to an imbalance, forcing its stock to drop 68 percent to close at $2.375, down $5.125. (See BioWorld Today, March 14, 2001, and Jan. 10, 2001.)
Gwen Rosenberg, Alliance's vice president of corporate communications, said at the onset of Oxygent trials that the company's plan was to seek a broad indication for general surgery and cardiac bypass. "We have not made a decision whether or not to continue the cardiac study," she said. "The general surgery data is hard data and the next step is to decide what we are going to do as far as clinical development goes. There's a possibility that we will go for a general surgery approval first and then revisit cardiac surgery in a few years. I expect we will be able to announce a clinical development plan in the May-June time frame."
Oxygent is comprised of liquid perfluorochemical (PFC) core particles surrounded by a surfactant and suspended in a water-based solution. The drug is fed into the patient's bloodstream and acts as blood would, picking up oxygen in the lungs and delivering it to tissues, then pulling carbon dioxide from the tissues and toting it back to the lungs for exhalation.
Alliance is developing the product in the U.S., Canada and Europe in conjunction with Deerfield, Ill.-based Baxter Healthcare Corp.
"Oxygent cannot carry viruses because it has no human or animal component - it is a sterile product, which is something that you cannot have with blood or hemoglobin that has been separated from blood," Rosenberg said. The oxygen carrier also has a shelf life of about two years vs. six weeks for donor blood and it does not require blood typing. Oxygent is made from raw materials that are available in large scale and it has a well-defined manufacturing process allowing it to be a cost-effective alternative to donor blood, she said.
Patients enrolled in the Phase III surgery study were undergoing orthopedic, urologic, abdominal, vascular, and other major procedures, many due to malignant disease, at 34 medical centers in eight European countries. The control and treatment patients had similar hemoglobin values at study entry and discharge. Oxygent was administered according to Alliance's patented Augmented-Acute Normovolemic Hemodilution (Augmented-ANH) technique. Blood usage, which consisted of either allogeneic (donor) blood or stored blood that was predonated by the patient, was compared for patients who received Oxygent in conjunction with the Augmented-ANH technique vs. standard transfusion therapy.
The target group was defined as patients for whom a transfusion was most likely to be needed. Two-thirds of the study patients (N=330) met the criteria, experiencing from 20 ml to more than 80 ml blood loss per kilogram of body weight. The benefit provided by Oxygent treatment was particularly evident in this population, a statement released by the company said.
In regard to transfusion avoidance, almost twice as many patients in the target group completely avoided the need for a transfusion compared to the control group, an approximately 100 percent relative improvement in blood avoidance. For patients who did not need blood, those in the target group who received Oxygent required an average of only two units of blood, compared to four units of blood for the control patients. Both the avoidance (p=0.006) and reduction (p<0.001) benefits were statistically significant through hospital discharge.
"The fact that Oxygent was able to reduce the amount of blood that the patients needed is valuable both for those patients individually and for society as a whole," Rosenberg said. "We certainly would like to be able to help augment the blood supply. There are shortages that are being experienced throughout the U.S. and elsewhere and this product could help support the blood supply."
Alliance's products are intended primarily for use during acute care situations including surgical, cardiology and respiratory applications.
Imavist, an ultrasound contrast agent being developed by Alliance in conjunction with Schering AG, of Germany, was the subject of a new drug application that has been reviewed by the FDA and found to be approvable, upon satisfactory response to certain issues identified in the review process. Rosenberg said approval is expected later this year.
In December, Alliance completed patient enrollment for an international Phase II/III study of LiquiVent, an intrapulmonary "liquid ventilation" agent for treatment of acute lung injury and acute respiratory distress syndrome. Results of this study should be announced in late May.