CAMBRIDGE, Mass., July 12 /PRNewswire-FirstCall/ -- Biopure Corporation today commented on articles published in the Wall Street Journal on July 6, 11, and 12, 2006. The articles reference adverse events in prior surgery trials of Biopure’s investigational oxygen therapeutic Hemopure(R) [hemoglobin glutamer - 250 (bovine)] and their potential significance in relation to two key events: the marketing application Biopure filed in the United Kingdom for the treatment of acutely anemic orthopedic surgery patients under age 80, and the Food and Drug Administration’s upcoming Blood Products Advisory Committee (BPAC) meeting to discuss the Navy’s proposed RESUS clinical trial of Hemopure for out-of-hospital treatment of trauma patients with acute blood loss. The company’s comments also correct misperceptions about why the BPAC meeting is being held in closed session.
To avoid pre-empting discussion of issues that may arise at the BPAC meeting, Biopure has generally avoided responding on the record to recent media inquiries. However, in response to what Biopure perceived to be an imbalanced perspective, the company recently provided contextual information on the record. Because this information was not addressed in recent articles, the company is issuing the following comments:
Clinical trials are conducted to identify the circumstances under which the benefit of an investigational product (in this case, a potential first-in- class product) exceeds the risks, so that appropriate guidelines such as patient population, dosage, etc. can be applied to a product label and/or future study protocols. In such trials, safety is evaluated by counting adverse events, but not all adverse events are test-agent related.
Orthopedic Surgery
In a previously completed Phase III trial of Hemopure versus red blood cell transfusion in the treatment of acutely anemic orthopedic surgery patients, 40 percent of the patients in the Hemopure arm were “crossover” patients who received both Hemopure and allogenic red blood cells. In this trial and in the integrated safety database of all Hemopure trials, the difference in the incidence of serious adverse events between patient groups largely disappears when sub-group stratification is done, such as eliminating patients over age 80 or removing the “crossover” patients. There were also differences in fluid volume management between patient groups, which led to more fluid overload in the Hemopure group, hence more cardiac/respiratory events, particularly in patients over age 80.
The marketing authorization application Biopure recently submitted in the United Kingdom is the company’s first such application in Europe and incorporates the considerable work that has been done to address questions arising from the Phase III orthopedic surgery trial. In preparing this submission, the company included new analyses of existing data and also provided data to and consulted with leading academic medical experts, regulatory advisors and regulatory authorities in Europe.
Biopure anticipates that a report on the Phase III orthopedic surgery trial, data from which were previously presented at medical meetings, will be submitted in a few weeks to a peer-reviewed journal for publication.
Out-of-Hospital Trauma
With regard to the Navy’s proposed RESUS trauma trial, the treatment of hemorrhagic shock outside the hospital is a very different clinical setting than elective orthopedic surgery in the hospital. RESUS is designed to investigate whether “life can be saved” in the out-of-hospital setting, where donor blood is not available, while the orthopedic surgery trial was designed to see if blood transfusion could be avoided. The risk-benefit equation is very different in the out-of-hospital trauma setting. Moreover, the proposed RESUS protocol includes measures to maximize this risk-benefit equation, including the following:
* RESUS targets patients who are in an acutely critical physiologic state -- e.g, they are generally hypotensive (critically low blood pressure) indicating hypovolemia (low blood volume);
* In RESUS, Hemopure would be used only during transport to the emergency room, where standard care would then be administered (including blood if indicated);
* RESUS currently targets a high-risk patient population with a much higher historical mortality than the orthopedic surgery population;
* RESUS contains well-defined inclusion/exclusion criteria, treatment guidelines and paramedic training regimens;
* RESUS has been defined and modified under the direction of a panel of military and academic experts from various disciplines such as trauma, emergency medicine, critical care, etc.
Importantly, there is also a strong preclinical basis for proceeding with RESUS, based on published and unpublished studies in various animal models of hemorrhagic shock conducted at various institutions by various investigators. These studies strongly support the hypothesis that, in an out-of-hospital trauma situation, Hemopure may be a superior resuscitative fluid than current non-oxygen carrying solutions. Biopure believes the opportunity to explore this premise in a well-designed clinical trial is valid when there are patients at risk who, data suggest, may benefit from Hemopure.
Because patients would be unconscious or traumatized, the trial design provides an exception from informed consent and a community consultation and disclosure process, as defined in FDA regulation 21 CFR 50.24.
FDA Blood Products Advisory Committee Meeting
Regarding the upcoming BPAC meeting being held in closed session, the company is completing and correcting the record as follows:
* Biopure knows of no precedent where an advisory committee meeting to discuss an investigational clinical trial proposal was held in open session. Open meetings are typically held to discuss new drug or biologic applications under review for marketing approval.
* Neither the FDA, Biopure nor the Navy insisted on a closed meeting. The FDA provided Biopure and the Navy with the agency’s requirements for conducting either an open or closed meeting. For an open meeting, both Biopure and the Navy would be required to sign waivers permitting the FDA to publicly disclose confidential information.
* The preparation time and submission deadlines differ for open and closed advisory committee meetings. For open meetings, longer lead times are required for preparing and editing materials to preserve confidentiality where necessary.
* Biopure considered signing such a waiver for clinical and preclinical data, excluding manufacturing and other proprietary information, but did not complete a waiver. There was concern that the prerequisites for an open meeting could have significantly delayed the meeting. Therefore, in order to
focus on substantive preparations, Biopure and the Navy agreed that the meeting would be held in closed session.
* In order for the proposed RESUS trial to proceed, FDA must lift the clinical hold and the Department of Defense (DoD) and the institutional review boards of participating hospitals in the communities where the study would take place must provide final authorization.
* If the clinical hold is lifted and DoD approval obtained, the details of the proposed trial and the product’s potential risks and benefits for the out- of-hospital treatment of trauma patients with acute blood loss would be made publicly available through a clinical trial website and extensive community notification activities.
Biopure Corporation
Biopure Corporation develops, manufactures and markets pharmaceuticals, called oxygen therapeutics, that are intravenously administered to deliver oxygen to the body’s tissues. Hemopure(R) [hemoglobin glutamer - 250 (bovine)], or HBOC-201, is approved for sale in South Africa for the treatment of surgical patients who are acutely anemic. Biopure has applied in the United Kingdom for regulatory approval of a proposed orthopedic surgical anemia indication. The company is developing Hemopure for a potential indication in cardiovascular ischemia, in addition to supporting the U.S. Navy’s government-funded efforts to develop a potential out-of-hospital trauma indication. The company’s veterinary product Oxyglobin(R) [hemoglobin glutamer - 200 (bovine)], or HBOC-301, the only oxygen therapeutic approved by the U.S. Food and Drug Administration and the European Commission, is indicated for the treatment of anemia in dogs. Biopure has sold approximately 177,000 units of Oxyglobin, which have been used to treat an estimated 90,000 animals.
The content of this announcement does not necessarily reflect the position or the policy of the U.S. Government or the Department of Defense, and no official endorsement should be inferred.
Statements in this announcement that are not strictly historical are forward-looking statements, including those that might imply that the proposed RESUS trauma trial will be allowed to proceed or that the marketing application for Hemopure in the United Kingdom will be accepted for review, will receive marketing authorization or will result in substantial sales. Actual results and their timing may differ materially from those projected in these forward-looking statements due to risks and uncertainties. These risks include, without limitation, uncertainties regarding the company’s financial position, unexpected costs and expenses, delays and determinations by regulatory authorities, unanticipated problems with the product’s commercial use, whether or not product related, and with product distributors, sales agents or other third parties, and delays in or unpredictable outcomes of clinical trials. The company undertakes no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof. A full discussion of the company’s operations and financial condition can be found in the company’s filings with the U.S. Securities and Exchange Commission, including under the heading “Risk Factors” in the Form 10-Q filed on June 9, 2006, which can be accessed in the EDGAR database at the SEC Web site, http://www.sec.gov.
Contact: Douglas Sayles Herb Lanzet (Investors) Biopure Corporation H.L. Lanzet Inc. (617) 234-6826 (212) 888-4570 IR@biopure.comlanzet@aol.com
Biopure Corporation
CONTACT: Douglas Sayles of Biopure Corporation, +1-617-234-6826, orIR@biopure.com; Herb Lanzet (Investors), H.L. Lanzet Inc., +1-212-888-4570,or lanzet@aol.com
Web site: http://www.biopure.com/
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