Three-Year Data from Phase 2 Trial of Genzyme Gaucher Disease Oral Compound Suggest Sustained or Further Improvement

Three-Year Data from Phase 2 Trial of Genzyme Gaucher Disease Oral Compound Suggest Sustained or Further Improvement Across All Endpoints
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme Corporation (NASDAQ: GENZ) today announced three-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. Sustained or further improvements were observed across all endpoints, including bone disease, at the three-year timepoint. The results were presented for the first time this week at the Lysosomal Disease Network WORLD Symposium in Las Vegas, Nevada.

Genzyme previously reported that the eliglustat tartrate phase 2 trial had met its primary endpoint at one year, and that data demonstrated continued improvement through two years. The primary composite endpoint was a clinically meaningful response in at least two of three endpoints: improvements in spleen size, hemoglobin and platelet levels. The study has continued with 19 patients through three years. The extension phase of this trial is still ongoing.

Eliglustat tartrate continued to show robust clinical response through three years:

Spleen volume decreased from baseline by a mean of 61 percent and liver volume decreased from baseline by 29 percent.
Hemoglobin level increased from baseline by a mean of 2.6 grams per deciliter.
Platelet count increased from baseline by a mean of 91 percent.
The study also analyzed the clinical response of patients in the phase 2 trial with respect to achieving therapeutic goals. Due to the heterogeneity of Gaucher disease, therapeutic goals were previously developed by experts involved in the treatment of Gaucher patients to assess their response to enzyme replacement therapy (ERT). Most patients dosed with eliglustat tartrate met established therapeutic goals for hemoglobin, platelets, spleen volume and liver volume, demonstrating progressive and clinically meaningful responses in multiple organ systems. At three years, 100 percent of patients met at least 3 of the 4 therapeutic goals developed for hematologic and organ volume parameters.

The three-year data also included analyses that suggest eliglustat tartrate positively impacts indicators of bone disease through three years of follow up. These indicators include bone mineral density in the lumbar spine, as measured by dual energy x-ray absorptiometry (DXA), and dark marrow signal in the femur, as visualized by magnetic resonance imaging (MRI). Dark marrow reflects the infiltration of lipid-laden Gaucher cells into bone marrow. Specifically:

In the 18 patients at baseline with dark marrow in the femur visible by MRI, five improved by one year, seven by two years and 10 by three years, with the other eight patients remaining stable.
In the 15 patients with results available at all time points, bone mineral density in the lumbar spine showed clinically and statistically significant improvements after one year of treatment (T score = +0.4) which further improved after 2 years (T score = +0.6) and were sustained after three years of treatment.
Ravi S. Kamath, M.D., Ph.D., Staff Radiologist at Massachusetts General Hospital and Instructor in Radiology at Harvard Medical School, who is the central radiology reviewer for the phase 2 study, said, "These data suggest that eliglustat tartrate may have a meaningful clinical impact on bone disease in Gaucher disease type 1 patients."

The most common adverse events (AEs) reported in greater than 2 patients through three years included viral infections (six patients), urinary tract infections and upper respiratory infections (4 patients each), headache, increased blood pressure, diarrhea and abdominal pain (three patients each). Eight drug-related AEs, including one serious event, were reported in six patients. Most AEs overall and all drug-related AEs were considered mild. The largest number of AEs was reported during the first 3 months of treatment.

"For thirty years, Genzyme has pioneered treatments for patients with lysosomal storage disorders, including the very first enzyme replacement therapy for Gaucher disease," said Genzyme's President, Personalized Genetic Health, John P. Butler. "Our momentum continues through the phase 3 trials - the largest ever conducted for Gaucher - as we build upon our foundation and commitment to Gaucher and look to extend the therapeutic options available to patients and physicians."

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 is currently enrolling patients in three global, multi-center, phase 3 trials of eliglustat tartrate. This is the largest clinical program ever focused on Gaucher disease, with over 50 sites in more than 25 countries currently participating. Genzyme's Gaucher disease portfolio also offers Cerezyme® (imiglucerase for injection), the standard of care for patients with Gaucher disease type 1, which is administered through intravenous infusions.

To learn more about the phase 3 trials of eliglustat tartrate, contact Genzyme Medical Information at [email protected] or 1-800-745-4447. More information can also be found at or

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, acid 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 typically affect the nervous system and brain.

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, M.D. 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 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. Over 300 subjects have now been treated in nine separate studies.

The data from the phase 2 trials with eliglustat tartrate were previously published in the journal Blood and the results can be found at the below references:

Phase 2 data at the 1 year time point: Lukina et al. Blood, Aug 2010; Vol. 116: 893 - 899
Phase 2 data at the 2 year time point: Lukina et al. Blood, Nov 2010; Vol 116: 4095 - 4098
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 2 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 approximately 10,000 employees in locations spanning the globe.

With many established products and services helping patients in 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. 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.

Important Information

Genzyme has filed with the Securities and Exchange Commission a Solicitation/Recommendation Statement on Schedule 14D-9 relating to the tender offer by Sanofi-Aventis. Genzyme shareholders are advised to read the company's Solicitation/Recommendation Statement on Schedule 14D-9 because it contains important information. Shareholders may obtain a free copy of the Solicitation/Recommendation Statement on Schedule 14D-9, as well as any other documents filed by Genzyme in connection with the tender offer, free of charge at the SEC's website at In addition, investors can obtain free copies of these documents from Genzyme by directing a request to Genzyme at 500 Kendall Street, Cambridge, MA 02142, Attention: Shareholder Relations Department, or by calling 617-252-7500 and asking for the Shareholder Relations Department.

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