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.
suggest that eliglustat tartrate may have a meaningful clinical impact
on bone disease in Gaucher disease type 1 patients.”
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
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
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 firstname.lastname@example.org
or 1-800-745-4447. More information can also be found at www.clinicaltrials.gov
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
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 www.genzyme.com.
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