FRAMINGHAM and CAMBRIDGE, Mass., May 13, 1998 -- Genzyme Transgenics Corporation (Nasdaq:GZTC) and Genzyme General (Nasdaq:GENZ) today announced they have initiated three phase III clinical trials with recombinant human antithrombin III (rh AT III), a transgenically-produced anti-clotting therapeutic. Previous phase I and phase II studies supported the safety of rh AT III at all administered doses and indicated its potential to improve the anticoagulation response to heparin in CABG (coronary artery bypass grafting) patients on cardiopulmonary bypass (CPB). CABG patients on CPB develop acquired AT III deficiency and therefore represent a model for this condition.
Acquired AT III deficiency occurs in many additional disease states, including liver disease, disseminated intravascular coagulation, septicemia, shock, burns, multiple trauma, bone marrow and other organ transplantation and surgical procedures. The only commercially-available AT III is derived from donor blood plasma, and is on the market in the United States for treatment of hereditary AT III deficiency and in Europe and Japan for acquired AT III deficiency disorders. Pivotal Study Design, Objectives and Rationale Two identical pivotal trials will evaluate the safety and efficacy of rh AT III, as compared to a placebo, in restoring heparin sensitivity to heparin-resistant patients scheduled for elective cardiac surgery requiring CPB. Patients on CPB require anticoagulation with heparin to prevent clotting, which occurs when blood comes into contact with the foreign surface of the CPB circuit. Heparin resistance is defined as a failure to achieve a desired level of anticoagulation following heparin administration. The degree of anticoagulation is monitored by the activated clotting time (ACT), which must reach a specified level before the patient can be put on bypass. These studies will seek to establish that administration of rh AT III to heparin-resistant patients will restore heparin responsiveness and thereby decrease the need for fresh frozen plasma in the management of heparin resistance. Each of the trials will be separate, double-blind, and randomized, and will enroll 52 patients. One multicenter trial will be performed in the US and the other in Europe. A third trial is designed to determine whether rh AT III matches, at equivalent doses, plasma-derived AT III's ability to restore heparin sensitivity among heparin-resistant patients undergoing CPB. This multicenter trial will enroll approximately 378 patients and be carried out in the United States and Europe. Patients will be randomly assigned to receive rh AT III at one of two dosage levels, or plasma-derived AT III at a dose equivalent to the lower rh AT III dose. Two dosage levels are being tested to compare the effects of high and low doses of rh AT III on heparin sensitivity and thrombin inhibition in patients receiving the same heparin dose. The pivotal trials are expected to require about one year to complete after enrollment of the first patient. "These trials mark the first time that a transgenically-produced therapeutic protein has entered pivotal clinical trials," said James A. Geraghty, Genzyme Transgenics' chairman. "Positive results in these studies will allow us to bring rh AT III to market in the year 2000, pending U.S. Food and Drug Administration approval." Genzyme Transgenics and Genzyme General have established a joint venture for the development, marketing and distribution of rh AT III in the United States and Europe. The companies are developing transgenic rh AT III initially for use in patients who demonstrate heparin resistance. The companies believe that rh AT III may be safer than the current plasma-derived version and could ultimately replace it in current clinical applications. In addition, wider availability of transgenic rh AT III could potentially allow its use in new applications. Transgenic proteins are produced by inserting human DNA into animal cells so that the target protein, or drug, is secreted into the milk of female offspring during lactation. Genzyme Transgenics produces rh AT III in the milk of transgenic goats at its 168-acre commercial production facility in central Massachusetts. Genzyme Transgenics Corp. applies transgenic technology to enable the development and production of recombinant proteins and monoclonal antibodies for medical uses. Primedica Corporation, Genzyme Transgenics' contract research organization, provides preclinical development and testing services to pharmaceutical, biotechnology, medical device and other companies. Genzyme Transgenics Corporation is also developing idiotypic vaccines in collaboration with the National Cancer Institute. Genzyme General develops and markets therapeutic and surgical products and diagnostic products and services. A division of the biotechnology and health care products company, Genzyme Corp., Genzyme General has its own common stock intended to reflect its value and track its performance. Genzyme General owns approximately 43 percent of the outstanding stock of Genzyme Transgenics. This news release contains forward-looking information, including statements about the timing and potential outcome of the pivotal clinical trials with rh AT III, the market launch date of rh AT III, and potential indications for rh AT III. Actual results may differ materially from these projections depending on the actual results and timing of clinical trials, the timing and content of decisions made by the U.S. Food and Drug Administration, and the accuracy of the companies' market research and information about potential new indications, and market acceptance of rh AT III.
CONTACT:
Genzyme Transgenics Corporation
Patricia F. Dimond, Ph.D.
Director of Corporate Development
and Communications
(508) 270-2374
Jonathan M. Nugent (investors)
Justin Jackson (media)
(212) 213-0006
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