Genzyme General and Pharming Group Report Results From First Two Clinical Trials for Pompe Disease.

Business Editors

LEIDEN, The Netherlands--(BUSINESS WIRE)--Oct. 6, 2000

Genzyme General (Nasdaq: GENZ) and Pharming Group N.V. (AEX: PHAR and EASDAQ: PHAR) announced today that results from the first two clinical trials ever conducted for Pompe disease were presented this week at the American Society of Human Genetics (ASHG) meeting in Philadelphia. Genzyme and Pharming are working in partnership to develop a treatment for Pompe disease and are associated with both clinical studies.

There is currently no effective therapy for patients who have Pompe disease, a rare and fatal genetic disorder caused by the lack of the lysosomal enzyme alpha-Glucosidase, which breaks down glycogen into glucose. The accumulation of glycogen in the heart and skeletal muscles of patients results in severe organ and tissue degradation. Pompe disease manifests itself in early or late-onset forms. Infants generally die before reaching 12 months of age, and the disease is typically fatal for those who develop symptoms as juveniles. Pompe disease affects an estimated 5,000-10,000 people in the developed world.

"Following the very successful clinical trial performed by Dr. A.T. van der Ploeg in Rotterdam, the encouraging results announced by Dr. Y.T. Chen confirm once more that Genzyme and Pharming are on the right track in developing a therapy for Pompe disease," according to George J.M. Hersbach, president and chief executive officer of Pharming Group N.V. "All parties involved are strongly committed to developing a therapy for Pompe, and these clinical results again bring us closer to making that much-needed therapy available to the patients who are suffering from this devastating disease."

On Tuesday, Y.T. Chen, M.D., Ph.D., of Duke University presented results from an ongoing Phase 1-2 study being conducted at Duke Medical Center, in which three infants with Pompe disease have received enzyme replacement therapy for over one year. The patients have been receiving intravenous infusions of a recombinant form of the enzyme human alpha-Glucosidase produced in CHO cells.

The preliminary results from the trial indicate that the product is capable of improving cardiac and skeletal muscle functions. In two patients, left ventricular mass measurements decreased during therapy. The infants have each passed the critical age of one year (currently 15-, 17-, and 20-months old) and continue to show improved cardiac function, thus averting the progressive cardiomyopathy and heart failure that normally lead to death prior to age one in untreated patients.

Improvements of skeletal muscle functions have also been noted, although the significance and extent have been more variable than with improvements in cardiac function. One patient showed marked improvement and currently has normal muscle tone and strength, as well as normal neurological and motor development evaluations. Muscle biopsies confirmed that significant reductions in glycogen accumulation occurred in one patient after enzyme replacement therapy. The study data showed that the CHO-cell product was generally well tolerated.

Also at the ASHG meeting, Dr. Ans T. van der Ploeg of Sophia Children's Hospital in Rotterdam presented the results from a 36-week Phase 2 clinical trial of transgenic human alpha-Glucosidase. The trial results were published in The Lancet in July. The study was sponsored by Genzyme and Pharming.

In the trial, four infants with Pompe disease ranging in age from 2.5 to 8 months received weekly infusions of transgenic human alpha-Glucosidase. The starting dose was 15-20 milligrams of enzyme per kilogram of body weight. The dose was later increased to 40 mg/kg.

Results showed that transgenic human alpha-Glucosidase lowered lysosomal glycogen storage and improved tissue morphology. Total tissue glycogen content did not change. Skeletal muscle and strength improved, most significantly for the patient who had the least severe disease at the start of treatment. This infant reached milestones that are beyond expectations for a patient with the disease, including crawling and standing with the support of one arm at the age of 12 months. Improvements in motor function were also observed for all patients.

The most prominent effect of treatment was on the heart. By 36 weeks, cardiac size had decreased significantly to less than 30 percent of baseline. Left-ventricular posterior-wall thickness and left-ventricular mass index decreased in all patients. All patients remain on therapy and have been treated for over a year. Adverse events such as fever, rashes, and flushing were transient and manageable by adaptation of the infusion rate and premedication. Patient enrollment in the clinical trial evaluating the use of transgenic alpha-Glucosidase has been completed. All patients will continue to receive treatment with the transgenic product and will have the option of transitioning to the CHO-cell derived product.

Earlier this year, Genzyme obtained exclusive, worldwide rights from Synpac (North Carolina) Inc. to develop and commercialize the human alpha-Glucosidase product derived from CHO cells, shifting its focus from the development of human alpha-Glucosidase produced in the milk of transgenic rabbits. The decision to pursue the CHO-cell product was based on manufacturing considerations. Genzyme and Pharming believe that the CHO-derived product can be scaled to commercial production levels, qualified for use, and made accessible to patients faster than the transgenic product. This decision was not based on efficacy or safety concerns with either product. Clinical results obtained to date suggest that the CHO-derived and transgenic products show comparable clinical effects.

Genzyme and Pharming plan to initiate a second clinical trial of the CHO-cell product by the end of 2000 in patients with infantile-onset Pompe disease. The companies are currently in discussions with the U.S. Food and Drug Administration on the design of the trial, which is expected to involve medical centers in both the United States and Europe. Further details will be announced later this fall once the trial's protocol has been finalized.

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 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.

Pharming focuses on the development, production and commercialization of human therapeutic proteins to be used in highly innovative therapies. Pharming has developed a proprietary production platform of transgenic animals, capable of producing human therapeutic proteins at high levels in their milk. The company's product portfolio is aimed at treatments for genetic disorders, surgery and trauma, infectious and inflammatory diseases, tissue and bone repair and blood-related disorders. Pharming has operations in Belgium, Finland, the Netherlands and the USA and currently employs more than 200 people.

This press release contains forward-looking statements, including statements about: the estimated Pompe disease patient population; plans to complete development of a treatment for Pompe disease; and the expected timing and design of a clinical trial. Actual results may materially differ due to numerous factors, including: the actual timing and content of decisions made by the FDA and other regulatory authorities; the results of clinical trial; the actual safety and efficacy of the therapy; the ability to manufacture sufficient quantities of product for development and commercialization activities; the accuracy of Genzyme's information about the Pompe disease patient population; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation Exhibit 99.2 to Genzyme's 1999 Annual Report on Form 10-K, as amended. GENZ stock is a series of common stock of Genzyme Corporation. Therefore, GENZ shareholders are subject to all of the risks and uncertainties described in the aforementioned reports.