It has been 18 months since this trial was stopped. Something is wrong with this system!
; January 8, 2001--- Alliance Pharmaceutical Corp. (NASDAQ-ALLP) announced today that it has voluntarily suspended enrollment in its Phase 3 cardiac surgery study with OxygentTM (perflubron emulsion) due to an imbalance in certain adverse events (AEs), primarily the incidence of stroke. While the frequency of these AEs in the Oxygent treatment group is in agreement with published data for patients undergoing cardiac bypass surgery, the control group frequency is remarkably low, causing a disparity in the proportion of AEs between the treatment and control patients. The study investigators have not attributed the AEs to the use of Oxygent, which has now been evaluated in 19 clinical studies involving more than 1,400 subjects. The AEs that prompted the suspension of the study were not apparent in a completed Phase 3 study with 492 general surgery patients that demonstrated significant reduction and avoidance in blood usage compared to the control population.
The suspended study was designed to evaluate the use of Oxygent in conjunction with hemodilution in 600 cardiac surgery patients undergoing coronary artery bypass grafting (CABG) procedures with cardiopulmonary bypass (CPB) support. The study design was based on Phase 2 CPB studies that did not exhibit similar safety imbalances. Differences between the Phase 2 and Phase 3 CPB studies included an increased level of hemodilution and a study population with a higher degree of blood loss. In addition, the imbalance in the Phase 3 study may be confounded by the number of elderly patients with advanced cardiovascular disease, protocol deviations, and possible reporting bias related to the single-blinded design of the study. "Although the incidence of adverse events was within expectations in the treatment group, the imbalance versus the control group prompted us to suspend enrollment until we can analyze the data and determine why the discrepancy occurred," said Duane J. Roth, Chairman and CEO of Alliance. "We have notified the study Data Safety Monitoring Board and the Food and Drug Administration (FDA) of our decision.
"Approximately two-thirds of the 600 patients projected for inclusion in the study have been enrolled to date," Roth noted. "When the safety analysis is concluded, we will be able to decide whether to complete the present study with some modifications, discontinue the study and evaluate the efficacy data, or conduct a complementary study. As noted, the study investigators have not ascribed the AE profile to the use of Oxygent. If the imbalance is associated with the degree of hemodilution, for example, we may be able to modify the method to address the AEs."
San Diego, CA; March 13, 2001--- Alliance Pharmaceutical Corp. (NASDAQ - ALLP) announced today that preparations are underway for the continued development of OxygentTM (perflubron emulsion), an intravenous oxygen carrier. A preliminary analysis of safety data from a Phase 3 cardiac surgery study with Oxygent has shown that there is no evidence to link the product directly to an imbalance in certain adverse events (primarily stroke) that led to the voluntary suspension of enrollment in the study in January. As reported previously, the frequency of these adverse events (AEs) in the Oxygent treatment group was consistent with current clinical practice for patients undergoing cardiac bypass surgery, whereas the control group frequency was at the extreme low end of expectations. To date, neither the Company, the study investigators, the study Data Safety Monitoring Board (DSMB), nor independent expert consultants believe that Oxygent is causally implicated in the adverse findings. Instead, the AEs appear more related to the rapid harvesting of additional blood from the Oxygent-treated patients prior to surgery, as well as other methodological differences between the treatment and control groups. Alliance is developing Oxygent in the United States, Canada, and Europe in conjunction with Baxter Healthcare Corporation. Based on the preliminary analysis of the study data, the companies are working together to prepare a revised comprehensive international strategy for seeking regulatory approvals for Oxygent. A final report of the safety findings from the study and a revised international clinical and regulatory plan for Oxygent are expected to be available by the beginning of May. The companies anticipate meeting with regulatory authorities soon thereafter in order to re-initiate clinical studies
San Diego, CA; May 2, 2001 --- Alliance Pharmaceutical Corp. (NASDAQ - ALLP) announced today that its agreement with Baxter Healthcare Corporation for the continued development of OxygentTM (perflubron emulsion) is proceeding as the two companies finalize a comprehensive international plan for seeking regulatory approvals for the product. As a result of this plan, which includes a revised timeline for clinical development and product launch, Baxter and Alliance have agreed to modify their original payment schedule. Baxter will make a $4 million investment in Alliance Series F Preferred Stock today, and will make a $3 million investment later this month. In order to maintain its rights to the product, Baxter must invest an additional $23 million prior to the end of September.
San Diego, CA; August 2, 2001 --- Alliance Pharmaceutical Corp. (NASDAQ - ALLP) announced today that Alliance and Baxter Healthcare Corporation have met with the U.S. Food and Drug Administration (FDA) regarding the continuing clinical development of OxygentTM (perflubron emulsion), an intravascular oxygen carrier intended to reduce the need for donor blood. As reported previously, Oxygent treatment provided a statistically significant reduction and avoidance of donor blood usage in a Phase 3 study with 492 general surgery patients. A subsequent Phase 3 cardiac surgery study was suspended voluntarily earlier this year due to certain adverse events that the companies have concluded were not directly related to Oxygent, but resulted from procedures specified in the protocol. A data analysis that explained reasons for this imbalance has been presented to the FDA. A final report with additional analyses, including support for the design of a new study, will be submitted to the FDA later this year. Following this submission, the companies anticipate providing the FDA and international regulatory authorities with an expanded clinical development plan that includes a new pivotal Phase 3 study with general surgery patients
San Diego, CA; January 17, 2002 --- Alliance Pharmaceutical Corp. (NASDAQ - ALLP) announced today that it has submitted documents to the U.S. Food and Drug Administration (FDA) and to European regulatory authorities regarding resumption of clinical development of OxygentTM (perflubron emulsion). The regulatory submissions included an Interim Integrated Safety Summary (IISS) containing data from all clinical studies conducted with the product, as well as a new Phase 3 clinical plan. Oxygent, an intravascular oxygen carrier intended to avoid the need for donor blood, is being developed by Alliance in the United States, Canada, and Europe in conjunction with Baxter Healthcare Corporation. Following the regulatory submissions, Baxter made an additional investment of $2 million in Alliance convertible preferred stock. The $2 million payment is part of a previously reported $19 million obligation that will be paid to Alliance as certain milestones are met in order for Baxter to maintain its rights to the product.
San Diego, CA; March 26, 2002 --- Alliance Pharmaceutical Corp. (NASDAQ – ALLP) announced today that representatives from Alliance and Baxter Healthcare Corporation have met with selected European regulatory authorities to review the clinical development plans for OxygentTM (perflubron emulsion), an intravascular oxygen carrier intended to avoid the need for donor blood in elective surgery. Based on positive interactions at these meetings, the companies are now planning a pivotal European Phase 3 study involving general surgery patients undergoing various procedures. Oxygent is being developed by Alliance in the United States, Canada, and Europe in conjunction with Baxter.
The proposed study protocol was developed utilizing data from a successful international Phase 3 study with 492 surgical patients, which demonstrated that Oxygent and acute normovolemic hemodilution treatment provided a statistically significant reduction and avoidance of donor blood usage. The new pivotal study would focus on the use of Oxygent for patients undergoing various general surgery procedures that are expected to result in moderate blood loss that usually requires transfusion of donor blood. Patients will be randomized at the time a blood transfusion is deemed necessary according to a defined transfusion trigger. The acute normovolemic hemodilution technique will not be used in this study; instead, treatment patients will receive Oxygent, while control patients will receive blood. The primary endpoint of the study will be the avoidance of donor blood transfusions.
"We are looking forward to completing the development of Oxygent in Europe," said Duane J. Roth, Chairman and CEO of Alliance. "The results from the previous general surgery study were extremely helpful in enabling us to design a protocol in which Oxygent is used in the same manner as blood, and is administered when the patient needs a transfusion during the surgical procedure.”
As announced previously, the companies also intend to resume clinical development of Oxygent in the U.S. Active discussions are currently ongoing with the U.S. Food and Drug Administration (FDA) regarding the information package submitted to the agency in January. Details about the development plan for Oxygent in the U.S. will be finalized and communicated after the appropriate FDA discussions have been completed. |
