{1} Successfully Completes Phase 4 Study Of Fabrazyme

CAMBRIDGE, Mass., Sept. 9 /PRNewswire-FirstCall/ -- Genzyme Corp. announced today that it has successfully completed its principal Phase 4 study of Fabrazyme(R) (agalsidase beta) and performed a preliminary analysis of the results. Completing this study was one of several requirements specified by the Food and Drug Administration when it approved the product for the treatment of Fabry disease in April 2003. Fabry disease is a very rare and potentially fatal hereditary disorder that can lead to renal failure, heart disease and stroke.

Fabrazyme was approved in the United States under the FDA's accelerated approval mechanism, which allows the agency to expedite the approval of treatments for serious or life-threatening disorders. Accelerated approvals can be granted on the basis of clinical trials establishing that a product has an effect on a surrogate endpoint reasonably likely to predict clinical benefit. A Phase 4 study to verify clinical benefit is required in this case. Only the FDA can determine whether a Phase 4 study has demonstrated clinical benefit and whether a drug is safe and effective. This press release reports top-line results of the Phase 4 Fabrazyme study and makes no such claims.

Genzyme plans to submit a summary study report to the FDA this month. Once the FDA has reviewed the data, Genzyme will meet with the agency to discuss their assessment and review next steps. The company will also submit the study results to regulatory authorities in the European Union and certain other regions to fulfill post-approval commitments. Genzyme expects to file the results for labeling purposes early next year.

In January 2001, Genzyme initiated a multinational, multicenter, double- blind placebo-controlled Phase 4 study of Fabrazyme. The trial enrolled 82 Fabry patients, both male and female, with mild to moderate renal disease. Patients were randomized 2:1 at each trial site to receive Fabrazyme at a dose of 1 mg/kg or a placebo. The trial's primary endpoint sought to determine whether Fabrazyme would reduce the rate of occurrence of certain clinically significant events that mark the advance of Fabry disease, namely the progression of renal, cardiac, or cerebrovascular disease or death. A substantially lower rate of these events was observed among the patients receiving Fabrazyme compared with the placebo patients. This trend was consistent among renal, cardiac and cerebrovasular events, despite the study's small sample size.

A prospectively defined analysis of study results revealed that, at baseline, a larger proportion of patients receiving Fabrazyme were found to have high proteinuria (protein in the urine), an established predictor of renal and cardiovascular disease and the most important determinant of outcomes in this study. As described by the study protocol, an adjustment was made to correct for this imbalance. This analysis found that, among the 82 patients enrolled in the study (the intent-to-treat population), those who received Fabrazyme were 53 percent less likely than the placebo patients to experience a clinically significant event (p=0.058). Among the 74 patients who were compliant with the study's protocol requirements (the per-protocol population), patients who received Fabrazyme were 61 percent less likely than the placebo patients to experience a clinically significant event (p=0.034). In the study, infusion reactions occurred at a higher rate in the treatment group and most frequently consisted of fever and chills. The incidence of serious adverse events in the study was similar among the treatment and placebo groups. (see "About Fabrazyme" below)

"Completing this study was a tremendous accomplishment, and we are sincerely grateful to the patients and physicians who participated," said Richard A. Moscicki, senior vice president and chief medical officer for Genzyme Corp. "We and many others-including members of the FDA advisory committee that evaluated Fabrazyme and the agency itself-identified the challenges inherent in conducting a placebo-controlled study for a progressive and potentially fatal disease when a treatment was commercially available."

Detailed results of the Phase 4 study of Fabrazyme will be presented at several scientific meetings next month. These include the 5th European Roundtable on Fabry Disease being held in Warsaw, and meetings of the American Society of Human Genetics in Toronto and the American Society for Nephrology in St. Louis.

Genzyme continues to work toward fulfilling additional post-approval commitments for Fabrazyme. These include the completion of an open-label extension study monitoring and evaluating the renal function of patients who participated in the principal Phase 4 study. Genzyme will also obtain long- term clinical status information on the Fabry population through the Fabry Registry it established three years ago to track the natural history and clinical outcomes of patients with Fabry disease, and it will complete its ongoing safety and pharmacodynamic study of Fabrazyme in pediatric patients.

About Fabrazyme

Fabrazyme is indicated for use in patients with Fabry disease. Fabrazyme reduces globotriaoscylceramide (GL-3) deposition in capillary endothelium of the kidney and certain other cell types. The reduction of GL-3 inclusions suggests that Fabrazyme may ameliorate disease expression; however, the relationship of GL-3 inclusion reduction to specific clinical manifestations of Fabry disease has not been established.

The most serious and common side effects reported with Fabrazyme are infusion reactions. Infusion reactions may include: increase in heart rate, increase in blood pressure up to a few hours after infusion, throat tightness, chest pain/tightness, shortness of breath, fever, chills, abdominal pain, itching, hives, nausea, vomiting, lip or ear swelling, rash, decrease in blood pressure, muscle pain, and headache. Infusion reactions occurred in many patients treated with Fabrazyme, and some of the reactions were severe. Anti- fever medications (for example, acetaminophen or ibuprofen) should be administered prior to infusion to reduce the potential for an infusion reaction. Infusion reactions occurred in some patients after receiving anti- fever medications, antihistamines and oral steroids. Because of the potential for severe infusion reactions, appropriate medical support measures should be readily available when Fabrazyme is administered. Patients with advanced Fabry disease may have compromised cardiac function, which may predispose them to a higher risk of severe complications from infusion reactions. Patients with compromised cardiac function should be monitored closely if the decision is made to administer Fabrazyme.

Other serious adverse events reported in the Phase 3 clinical trial of Fabrazyme included stroke, pain, ataxia, bradychardia, cardiac arrhthymia, cardiac arrest, decreased cardiac output, vertigo, hypocousia, and nephrotic syndrome. These adverse events also occur as manifestations of Fabry disease: an alteration in frequency or severity cannot currently be determined from the small numbers of patients studied

About Genzyme

Genzyme Corporation is a global biotechnology company dedicated to making a major positive impact on the lives of people with serious diseases. The company's broad product portfolio is focused on rare genetic disorders, renal disease, osteoarthritis and immune-mediated diseases, and includes an industry-leading array of diagnostic products and services. Genzyme's commitment to innovation continues today with research into novel approaches to cancer, heart disease, and other areas of unmet medical need. More than 6,300 Genzyme employees in offices around the globe serve patients in over 80 countries.

This press release contains forward-looking statements, including the statements regarding the timing of Genzyme's submission of a trial results to the FDA and other regulatory authorities, the timing of its meeting with the FDA, its intent to file the results for labeling purpose and the timing thereof, its plans to provide detailed results at several upcoming scientific meetings, and its continuation of several post-approval commitments. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others, those described in reports filed by Genzyme with the Securities and Exchange Commission under the Securities Exchange Act of 1934, as amended, including without limitation the information under the heading "Factors Affecting Future Operating Results" in the Management's Discussion and Analysis of Financial Condition and Results of Operations section of the Genzyme Quarterly Report on Form 10-Q for the period ended June 30, 2004. Genzyme cautions investors not to place substantial reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise the statements.

Genzyme's press releases and other company information are available at http://www.genzyme.com/ and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-703-797-1866 outside the United States.

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Genzyme Corp.