Alliance Pharmaceutical Corp. Announces Further Analysis of Oxygent Phase 3 Surgery Study Confirms Statistically Significant Reduction and Avoidance of Blood Usage
-- Patients who received Oxygent either completely avoided the need for blood more frequently than the control group, or required fewer units of blood than the controls:
SAN DIEGO--(BW HealthWire)--Dec. 11, 2000-- -- For the entire study population (492 patients), the
Oxygent benefit was statistically significant for both
avoidance of blood (p=0.038) and reduction in blood usage
(p=0.013).
For patients who had blood losses ranging from ~10 mL/kg to more than 80 mL/kg (86% of the study population), the Oxygent benefit was highly statistically significant for both avoidance of blood (p=0.002) and reduction in blood usage (p less than 0.001).
Transfusion avoidance and reduction remained statistically significant through the monitoring period of 21 days or hospital discharge.
Based on the impending completion of an additional Phase 3 study with cardiac surgery patients, Alliance and Baxter plan a comprehensive strategy for U.S. and European regulatory approvals.
Alliance Pharmaceutical Corp. (Nasdaq:ALLP - news) announced that further analysis of data from an international Phase 3 general surgery study with Oxygent(TM) (perflubron emulsion), an intravenous oxygen carrier, is being presented today at the 54th Postgraduate Assembly in Anesthesiology in New York by a principal investigator of the study, Prof. Donat R. Spahn, MD, from the Institute for Anesthesiology, University Hospital, Zurich. Dr. Spahn's presentation states that 86% of the patients enrolled in the study (424 of the total 492 patients screened for study inclusion) underwent major surgery resulting in about 10 milliliters of blood loss per kilogram body weight to more than 80 mL blood loss per kg body weight. Patients in this group who received Oxygent either completely avoided the need for blood more frequently than the control group, or required fewer units of blood than the controls. Both the avoidance and reduction of blood transfusions were statistically significant through the study monitoring period (the earlier of 21 days post-operation or day of hospital discharge). Oxygent is therefore the only oxygen carrier to date that has demonstrated clinical benefits in a Phase 3 study with patients undergoing a variety of general surgical procedures. Alliance is developing the product in the United States, Canada, and Europe in conjunction with Baxter Healthcare Corporation.
The Phase 3 study enrolled 492 patients undergoing orthopedic, urologic, abdominal, vascular, and other major surgical procedures, many due to malignant disease, at 34 medical centers in eight European countries. Oxygent was administered to the patients according to Alliance's patented Augmented-Acute Normovolemic Hemodilution(TM) (Augmented-ANH) technique. Blood usage, which consisted of either allogeneic (donor) blood or stored blood that was predonated by the patient during the weeks prior to surgery, was compared for patients who received Oxygent in conjunction with the Augmented-ANH technique vs. standard transfusion therapy.
For the 86% of the patients who experienced at least 10 mL/kg blood loss, Oxygent provided a highly statistically significant benefit on the day of surgery for both the primary study endpoint of transfusion reduction (p less than 0.001) and the secondary endpoint of avoidance (p=0.002) of blood usage. These benefits remained statistically significant through all monitoring timepoints post-surgery at day 3, day 7, and day 21 (or day of discharge), for both transfusion reduction and avoidance.
As reported previously, Oxygent provided a statistically significant benefit for the total study population of 492 patients. Analysis of data from the entire study population, including the 14% of the patients who had minimal blood loss not requiring transfusions (less than 10mL/kg), showed that the patients who received Oxygent required a statistically significant (p=0.013) fewer number of units of donor blood than the patients treated with standard transfusion therapy. Further, when all blood usage including allogeneic and predonated blood was accounted for in the entire 492-patient population, the Oxygent treatment group had a statistically significant (p=0.038) greater avoidance of blood transfusions than the control patients.
With regard to safety, the use of Oxygent as part of the Augmented-ANH technique was well tolerated. Reported side effects were limited to those expected in patients undergoing major surgery, the majority for malignant disease. The data indicated that the Augmented-ANH procedure with Oxygent should offer patients undergoing a diverse range of surgeries a favorable safety profile and a higher likelihood of avoiding blood transfusions. Detailed results from the study are planned for presentation at the European Society of Anesthesiology annual meeting to be held in Sweden in April.
In addition to this Phase 3 general surgery study, Oxygent is being evaluated in a Phase 3 study with cardiac surgery patients undergoing coronary artery bypass grafting (CABG) procedures with cardiopulmonary bypass (CPB) support. This study will involve a total of 600 patients, primarily at medical centers in the United States, with additional participation by hospitals in Canada and Europe. More than half of the patients have been enrolled to date, and completion of enrollment is projected for the first quarter of 2001. An independent Data Safety Monitoring Board has already evaluated safety data from 209 patients, and has recommended continuation of the study without modification.
``Oxygent is the only oxygen carrier that is being evaluated in both cardiac and general surgery Phase 3 studies,'' said Duane J. Roth, chairman and CEO of Alliance. ``This puts us in the unique position of potentially being able to achieve regulatory approvals for a broad surgical indication that includes the majority of elective surgery procedures wherein patients are at risk of receiving blood transfusions.
``Due to the positive results of the general surgery study and the progress of the cardiac surgery study, Alliance and Baxter have decided to take a comprehensive international approach to seeking regulatory approvals for Oxygent. We therefore intend to submit regulatory applications in both the United States and Europe that combine the data from the cardiac and general surgery populations, rather than submitting separate applications for each indication.
``This 'combined dossier' strategy has several advantages,'' Mr. Roth explained. ``First, it could accelerate the time to market for a broad surgical population, since we would anticipate market approval for two indications simultaneously. Second, it could speed acceptance of Oxygent by allowing educational activities to target a broad array of medical practitioners and patients upon approval of the product. Finally, the combined dossier enables us to provide the regulatory authorities with a compelling submission package containing data from more than 1,000 Phase 3 surgical patients.
``These advantages,'' Roth concluded, ``lead us to believe that the combined dossier strategy is the most expedient route to the approval and marketing of Oxygent to the largest possible initial patient population in both the United States and Europe.
``We are currently working on the sections of the regulatory applications that include the data from the general surgery study,'' Roth noted. ``We expect to have the cardiac data available mid-year, which would enable us to submit both a New Drug Application in the United States and a Marketing Authorization Application in Europe during the second half of 2001.''
Approximately 8 to 10 million surgeries are performed worldwide each year during which the patient requires transfusions of donor blood. ``We are excited about the potential for Oxygent to be an alternative to donor blood, which is in short supply in regions of the United States and Europe,'' Roth stated. ``There are three main considerations for an oxygen carrier to be able to address this need adequately -- it has to be proven safe and effective in clinical studies that involve various patient populations, it has to be manufactured in large quantities using economical processes, and it has to be marketed by an organization with experience and capability for international sales.
``Oxygent is well-positioned to satisfy all of these requirements,'' Roth explained. ``In the next few months we will have completed Phase 3 studies with both general and cardiac surgery patients. Oxygent's primary raw material is a synthetic perfluorochemical compound that is available in commercial quantities at relatively low cost, and can be manufactured into the final product using an efficient processing method. Our manufacturing facility has the capacity to produce about 800,000 units of Oxygent per year, and we plan to add production capability of at least an additional 3 million annual units in the next few years.
``Oxygent will be marketed by Baxter, a recognized leader in the sales and distribution of products for the surgical setting, including proprietary anesthesia and critical care products. The Baxter division that will market the product focuses on the anesthesiologist, the physician most responsible for transfusion decisions.
This makes them an ideal marketing partner for Oxygent.``
The Alliance and Baxter Healthcare Corporation agreement regarding Oxygent was established in May 2000. Baxter obtained an exclusive license for the manufacture, sales, and distribution of Oxygent in the United States, Canada, and Europe, and has the rights to co-develop Oxygent for further indications. Baxter's initial investment will help support Alliance in the completion of late-stage clinical trials and achievement of regulatory approvals.
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