Two-Year Data from Phase 2 Trial of Genzyme Gaucher Disease Oral Compound Suggest Continued Improvement Across All Endpoints

Two-Year Data from Phase 2 Trial of Genzyme Gaucher Disease Oral Compound Suggest Continued Improvement Across All Endpoints
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme Corporation (NASDAQ: GENZ) announced today two-year follow-up data from patients enrolled in the phase 2 clinical trial for its investigational oral therapy for Gaucher disease type 1 known as eliglustat tartrate (formerly Genz-112638). Continued improvements were observed across all endpoints, including bone disease, at the two-year timepoint, compared with baseline. The two-year results were presented for the first time today at the Lysosomal Disease Network WORLD Symposium in Miami, Fla.

"Bone disease is a primary cause of morbidity for patients with Gaucher disease"
Eliglustat tartrate, a capsule taken orally, is being developed to provide a convenient treatment alternative for adult patients with Gaucher disease type 1, and to offer a broader range of treatment options for patients and physicians to achieve individual therapeutic goals. Genzyme's Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher disease type 1, is administered through intravenous infusions.

Genzyme reported last year that the phase 2 trial had met its primary composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in spleen size, hemoglobin and platelet levels) in individual patients after the 52-week study period. Twenty-two of 26 study participants completed at least one year of treatment, and 20 patients completed two years of treatment. The study is continuing with 19 patients in their third year. Medical centers in North America, South America, Europe and the Middle East participated in this study.

Continued improvement was observed through two years for patients who received eliglustat tartrate:

Spleen volumes decreased from baseline by a mean of 52 percent and liver volumes decreased from baseline by 24 percent.
Hemoglobin levels increased from baseline by a mean of 2.1 grams per deciliter.
Platelet counts increased from baseline by a mean of 81 percent.
Chitotriosidase levels decreased from baseline by a median of 63 percent (only 18 month data are available to date), among the 17 patients with chitotriosidase. Chitotriosidase is commonly monitored by physicians as a biomarker of Gaucher disease burden and response to treatment.
"We remain committed to building our Gaucher health portfolio by developing clinically meaningful solutions to support individualized care for this community," said Genzyme Senior Vice President Geoff McDonough, MD. "We have set a high threshold for success for eliglustat tartrate, and are very encouraged by the results we continue to observe."

According to the ICGG Gaucher Registry, an international multi-center program sponsored by Genzyme that tracks the routine clinical outcomes for patients with Gaucher disease, irrespective of treatment status, over 80 percent of Gaucher patients have radiologic evidence of bone disease. The data presented today also included pre-planned analyses that suggest eliglustat tartrate may positively impact some indicators of bone disease through two years of follow up. These indicators include bone mineral density, as measured by dual energy x-ray absorptiometry (DXA), and the proportion of dark marrow on magnetic resonance imaging (MRI). Dark marrow reflects the infiltration of diseased cells into the bone marrow. Specifically:

Bone mineral density (BMD) in the lumbar spine showed clinically and statistically significant improvements (Z score = +0.60, T score = +0.56) in 16 patients with available data at baseline, one and two years. Four out of six of these patients who were below the normal range at baseline improved to have normal BMD Z scores at two years.
In the 18 patients with dark marrow visible on MRI at baseline, six improved by one year, an additional two improved by two years and 10 remained stable.
"Bone disease is a primary cause of morbidity for patients with Gaucher disease," continued Dr. McDonough. "These data suggest that eliglustat tartrate may have a significant effect on bone mineral density, which could make a positive impact on the lives of patients."

Eliglustat tartrate was generally well tolerated. The most common adverse events (AEs) reported in greater than 10 percent of patients by two years included viral infections (six patients), urinary tract infections, increased blood pressure, and abdominal pain (three patients each). Eight drug-related AEs, including one serious event, were reported in six patients. All were mild in severity.

Genzyme has begun enrollment in two global, multi-center, phase 3 trials of eliglustat tartrate. The first trial, ENCORE, is a randomized, open-label study for adult patients with Gaucher disease type 1 designed to compare eliglustat tartrate to Cerezyme. Adult patients who have previously received Cerezyme for at least three years and have reached their therapeutic goals may qualify for this trial. The second trial, ENGAGE, is a randomized, double-blind, placebo-controlled study for patients with a confirmed diagnosis of Gaucher disease type 1. Patients who have not been treated in the last 12 months for Gaucher disease may qualify for this study. Over 30 centers in more than 20 countries are participating in these trials. Genzyme is also initiating a trial comparing once-daily dosing of eliglustat tartrate with twice-daily dosing.

To learn more about these trials contact Genzyme Medical Information at [email protected] or 1-800-745-4447. More information can also be found at

About Gaucher disease

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, β-glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease, type 1, does not affect the brain or nervous system.

About eliglustat tartrate

Eliglustat tartrate, a novel glucosylceramide analog given orally, is designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease. In preclinical studies, the molecule, developed with James A. Shayman, MD, from the University of Michigan, has shown high potency and specificity. Based on its mechanism of action, which is independent of genotype, eliglustat tartrate may be a potential therapy for all patients with Gaucher disease type 1. Initiation of the Phase 2 and 3 studies of eliglustat tartrate in Gaucher disease followed completion of an extensive pre-clinical research effort and a Phase 1 program that involved more than 120 subjects in three separate studies. Safety analysis of the phase 2 trial demonstrated that eliglustat tartrate was well tolerated. The most common adverse events (AEs) by two years included viral infections, urinary tract infections, increased blood pressure and abdominal pain.

Cerezyme important safety information

Approximately 15 percent of patients have developed IgG antibodies, and these patients have a higher risk of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity occurred in 6.6 percent of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension. Reactions related to Cerezyme administration have been reported in less than 15 percent of patients. Each of the following events occurred in less than two percent of the total patient population. Reported adverse events include nausea, vomiting, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache and tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture. For full prescribing information, please visit

About Genzyme

One of the world's leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 12,000 employees in locations spanning the globe and 2008 revenues of $4.6 billion.

With many established products and services helping patients in approximately 100 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company's products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

Genzyme's press releases and other company information are available at and by calling Genzyme's investor information line at 1-800-905-4369 within the United States or 1-678-999-4572 outside the United States.

Genzyme® and Cerezyme® are registered trademarks of Genzyme Corporation. All rights reserved.

This press release contains forward looking statements regarding Genzyme's investigational therapy eliglustat tartrate including: that eliglustat tartrate will offer a broad range of treatment options to physicians and convenience to patients and that eliglustat tartrate could have a significant impact on bone mineral density and make a positive impact on patients' lives. These forward looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those forecasted. These risks and uncertainties include: that regulatory approval of eliglustat tartrate will be delayed or limited either in the United States or elsewhere, that eliglustat tartrate will not be available for patients' convenience and will not provide additional treatment options to physicians or patients; that eliglustat tartrate will not have a positive effect on bone mineral density or otherwise on bone disease and will not impact patients lives; 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 the information under the heading "Risk Factors" in Genzyme's Quarterly Report on Form 10-Q for the quarter ending September 30, 2009. 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 these statements.

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