Monday January 10, 6:59 am Eastern Time
Company Press Release
SOURCE: Genzyme General
Genzyme Transgenics and Genzyme General
Announce Phase III Data on rhATIII
-First Phase III Trial for Transgenically Produced Protein Meets Primary Endpoint-
FRAMINGHAM and CAMBRIDGE, Mass., Jan. 10 /PRNewswire/ -- Genzyme Transgenics (Nasdaq: GZTC - news) and
Genzyme General (Nasdaq: GENZ - news) today announced results of their phase III trial evaluating the ability of
transgenically produced recombinant human antithrombin III (rhATIII) to restore heparin sensitivity in heparin-resistant patients
undergoing elective heart surgery requiring cardiopulmonary bypass (CPB). The results were statistically significant (p=<0.001)
in meeting the trial's primary endpoint-reduction in the use of fresh frozen plasma.
As noted in Genzyme Transgenics' presentation at the Chase H&Q Healthcare Conference today, these results mark the first
time a transgenic drug candidate has advanced to and successfully completed a phase III clinical trial evaluation.
''The data indicate that transgenically produced rhATIII has the potential to support an extremely important function,
anticoagulation, in heparin- resistant patients undergoing cardiopulmonary bypass,'' said Jerrold Levy, M.D., director of
cardiothoracic anesthesiology, Emory University School of Medicine. ''The prospect of an unlimited supply of this unique
therapeutic protein may enable physicians to avoid the need for donor blood products. Transgenic proteins have the potential to
provide a new and exciting treatment option for the future.''
Patients undergoing cardiopulmonary bypass require anticoagulation with heparin to prevent clotting, which can occur when
blood comes into contact with the tubing and artificial surfaces of the heart-lung machine used to take over the heart's function
during surgery. Treatment of heparin-resistant patients with fresh frozen plasma is one option available to restore heparin
sensitivity and achieve adequate anticoagulation to permit initiation of cardiopulmonary bypass.
The results of the study demonstrated that in heparin-resistant patients, 21 percent, or 6 out of 28 patients in the rhATIII
treated group required fresh frozen plasma to manage their heparin resistance, compared to 92 percent, or 22 out of 24
patients in the placebo group. This result is statistically significant (p=0.001).
The double-blinded, randomized, placebo-controlled study, which was conducted under a U.S. IND, evaluated 52 patients at
six medical centers in Germany and the United Kingdom. This trial is the first of two identical phase III trials.
''We are pleased that the data demonstrate the biological activity of rhATIII in this setting and show its potential value,'' said
Sandra Nusinoff Lehrman, M.D., president and chief executive officer of Genzyme Transgenics. ''This result is a significant
milestone in the advancement of transgenic technology and we await the results of the second phase III trial to confirm these
results. In the future, we plan to conduct additional studies to further evaluate this compound for other potential uses.''
Additional Trial Results
In addition to achieving statistical significance on the primary endpoint, the trial also achieved statistical significance on two out
of three secondary endpoints. Secondary endpoints included maintenance of normal ATIII levels and changes in two
biochemical markers of coagulation: D-dimer and fibrin monomer.
In the treatment group, ATIII blood levels increased to 103 percent of normal 30 minutes after the start of surgery, and were at
104 percent of normal at the end of CPB. In contrast, ATIII levels in placebo patients who received fresh frozen plasma were
41 percent of normal within 30 minutes after the start of bypass, and were 42 percent of normal at the end of CPB.
Researchers report that they did not note any significant differences between the rhATIII and placebo groups with respect to
safety parameters. There was no evidence of antibody formation in the patients treated with rhATIII.
Trial Design
ATIII deficiency is a key factor in heparin resistance, since heparin requires ATIII for effective anticoagulation. Administration
of fresh frozen plasma, which contains ATIII, is one approach to managing heparin resistance. This trial was designed to
evaluate the potential efficacy of rhATIII to reduce the need for treatment with fresh frozen plasma.
The degree of anticoagulation during cardiopulmonary bypass is measured by the activated clotting time (ACT). An ACT of
480 seconds or greater reflects adequate anticoagulation for initiation and maintenance of CPB. In this study, after receiving a
total of 400U/kg heparin before CPB, patients whose ACT was still less than 480 seconds were randomized into either
rhATIII (75U/kg) or placebo groups. Following treatment, patients whose activated clotting time remained below 480 seconds
were given fresh frozen plasma. Background Information
Genzyme Transgenics and Genzyme General have established a joint venture, ATIII LLC, for the development, marketing, and
distribution of rhATIII in the United States and Europe. The companies believe that rhATIII may have significant advantages
over plasma ATIII, including unlimited availability and pricing flexibility, and that rhATIII could ultimately replace plasma ATIII
in current clinical applications. In addition, wider availability of rhATIII could potentially expand its use in new applications.
Genzyme Transgenics Corporation 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 General develops and markets therapeutic products and diagnostic products and services. Genzyme General has
three therapeutic products on the market and a strong pipeline of therapeutic products in development focused primarily on the
treatment of rare genetic diseases. A division of the biotechnology company Genzyme Corporation, Genzyme General has its
own common stock intended to reflect its value and track its economic performance.
This press release contains forward-looking statements, including statements concerning the potential use of rhATIII for CPB,
anticipated clinical trials, potential additional indications for rhATIII, and the anticipated advantages of rhATIII over plasma
ATIII. Actual results may materially differ due to numerous factors, including the results of the anticipated additional phase III
trial; the results of pre-clinical and clinical development efforts for additional indications; the safety and efficacy of the product;
the content of decisions by regulatory authorities; and market acceptance of rhATIII.
Genzyme's releases are available on the World Wide Web at genzyme.com. They are also available from
Genzyme's fax-on-demand service at 1-800-436-1443 within the United States or 1-201-521-1080 outside the United States.
Genzyme Transgenics' releases are available on the World Wide Web at transgenics.com.
SOURCE: Genzyme General |
