Genzyme Announces Positive New Data from Two Phase 3 Studies for Oral Eliglustat Tartrate for Gaucher Disease

Fri Feb 15, 2013 11:15am EST

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CAMBRIDGE, Mass.--(Business Wire)--
Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), today announced
positive new data from the Phase 3 ENGAGE and ENCORE studies of eliglustat
tartrate, its investigational oral therapy for Gaucher disease type 1. The
results from the ENGAGE study were presented today at the 9th Annual Lysosomal
Disease Network WORLD Symposium in Orlando, Fla. In conjunction with this
meeting, Genzyme also released topline data from its second Phase 3 study,
ENCORE. Both studies met their primary efficacy endpoints and together will form
the basis of Genzyme`s registration package for eliglustat tartrate. 

The company is developing eliglustat tartrate, a capsule taken orally, to
provide a convenient treatment alternative for patients with Gaucher disease
type 1 and to provide a broader range of treatment options for patients and
physicians. Genzyme`s clinical development program for eliglustat tartrate
represents the largest clinical program ever focused on Gaucher disease type 1
with approximately 400 patients treated in 30 countries. 

"The data presented at this year`s WORLD symposium reinforce our confidence that
eliglustat tartrate may become an important oral option for patients with
Gaucher disease," said Genzyme`s Head of Rare Diseases, Rogerio Vivaldi MD. "We
are excited about this therapy`s potential and are making excellent progress in
our robust development plan for bringing eliglustat tartrate to the market." 

ENGAGE Study Results:

In ENGAGE, a Phase 3 trial to evaluate the safety and efficacy of eliglustat
tartrate in 40 treatment-naïve patients with Gaucher disease type 1,
improvements were observed across all primary and secondary efficacy endpoints
over the 9-month study period. Results were reported today at the WORLD
Symposium by Pramod Mistry, MD, PhD, FRCP, Professor of Pediatrics & Internal
Medicine at Yale University School of Medicine, and an investigator in the

The randomized, double-blind, placebo-controlled study had a primary efficacy
endpoint of improvement in spleen size in patients treated with eliglustat
tartrate. Patients were stratified at baseline by spleen volume. In the study, a
statistically significant improvement in spleen size was observed at nine months
in patients treated with eliglustat tartrate compared with placebo. Spleen
volume in patients treated with eliglustat tartrate decreased from baseline by a
mean of 28 percent compared with a mean increase of two percent in placebo
patients, for an absolute difference of 30 percent (p<0.0001). 

Secondary endpoints also improved:

* Platelet levels increased from baseline by an absolute difference of 41
percent compared with placebo (P<0.0001) 
* Hemoglobin levels increased from baseline by an absolute difference of 1.2
g/dL compared with placebo (P<0.0006) 
* Liver volume decreased from baseline by an absolute difference of seven
percent compared with placebo (P<0.0072)

Among tertiary endpoints:

* A statistically significant improvement in total bone marrow burden was
observed among patients in the eliglustat tartrate arm compared to placebo, and
all other markers of bone disease showed trends towards improvement.

In the study, there were no serious adverse events reported in either treatment
group. All adverse events reported were mild or moderate, with the most common
being headache, arthralgia and diarrhea. One patient withdrew from the trial,
for a reason not treatment-related. At the end of the nine months, patients who
were on placebo were transitioned to eliglustat tartrate. 

ENCORE Study Results: 

ENCORE, the second Phase 3 trial in the eliglustat tartrate development program,
also met its primary efficacy endpoint. 

ENCORE is a multi-national, randomized, controlled, open-label, study designed
to determine whether eliglustat tartrate is non-inferior to Cerezyme®
(imiglucerase for injection). In the trial, 160 patients with Gaucher disease
type 1 who had begun enzyme replacement therapy at least three years prior to
randomization and who had reached therapeutic goals were randomized (2:1) to
receive either eliglustat tartrate or Cerezyme for one year. 

The primary efficacy endpoint of stability was a composite endpoint of
pre-specified change criteria for each of the following parameters: spleen
volume, hemoglobin levels, platelet counts, and liver volume. To meet the
endpoint for stability, a patient had to remain stable in all four parameters.
Eliglustat tartrate met the pre-specified criteria for non-inferiority to
Cerezyme, with the majority of patients in both groups remaining stable one year
after randomization (84 percent of eliglustat tartrate patients and 94 percent
of Cerezyme patients). 

In an additional, pre-specified, efficacy analysis of the percent change in
spleen volume from baseline, a mean change of minus six percent was observed in
the eliglustat tartrate arm compared with minus three percent in the Cerezyme
arm. This analysis also met the criteria for non-inferiority. 

With regard to secondary endpoints, after one year, nearly all patients
receiving eliglustat tartrate met the stability criteria for the individual
components of the composite endpoint:

* 94 percent of patients met spleen volume criteria 
* 95 percent of patients met hemoglobin levels criteria 
* 93 percent of patients met platelet levels criteria 
* 96 percent of patients met liver volume criteria

The majority of patients had normal bone mineral density scores at study entry
for total femur and lumbar spine. These scores were maintained over the 12-month
study period. 

In the ENCORE trial, two percent (n=2) of eliglustat tartrate patients and two
percent (n=1) of Cerezyme patients discontinued treatment because of an adverse
event. Over the course of one year, four adverse events were observed in the
eliglustat tartrate treatment group with ≥10 percent incidence compared with
Cerezyme: fatigue (14 percent overall incidence), headache (13 percent overall
incidence), nausea (12 percent overall incidence), and upper abdominal pain (10
percent overall incidence). The majority of adverse events (AEs) were mild or
moderate in severity for both groups. There were no serious adverse events in
the study that were considered to be related to therapy by the treating

The results from the ENCORE study are expected to be presented at a medical
meeting in the second half of the year. 

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, generally does not
affect the brain. 

About eliglustat tartrate

Eliglustat tartrate, a novel glucosylceramide analog given orally, was 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. The concept
was initially developed by the late Norman Radin, MD, from the University of
Michigan. In pre-clinical studies, the molecule, developed with James A.
Shayman, MD, also from the University of Michigan, has shown high potency and
specificity. Initiation of the Phase 2 and 3 studies of eliglustat tartrate in
Gaucher disease followed an extensive pre-clinical research effort and a Phase 1

Cerezyme Important Safety Information

Cerezyme (imiglucerase for injection) is indicated for long-term enzyme
replacement therapy for pediatric and adult patients with a confirmed diagnosis
of Type 1 Gaucher disease that results in one or more of the following
conditions: anemia (low red blood cell count), thrombocytopenia (low blood
platelet count), bone disease or hepatomegaly or splenomegaly (enlarged liver or

Approximately 15% of patients have developed immune responses (antibodies).
These patients have a higher risk of an allergic reaction (hypersensitivity).
Use Cerezyme (imiglucerase for injection) carefully if you have had an allergic
reaction to the product in the past. Symptoms suggestive of allergic reaction
happened in 6.6% of patients, and include anaphylactoid reaction (a serious
allergic reaction), itching, flushing, hives, an accumulation of fluid under the
skin, chest discomfort, shortness of breath, coughing, cyanosis (a bluish
discoloration of the skin due to diminished oxygen), and low blood pressure. 

Side effects related to Cerezyme administration have been reported in less than
15% of patients. Each of the following events occurred in less than 2% of the
total patient population. Reported side effects include nausea, abdominal pain,
vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache,
and rapid heart rate. Because Cerezyme therapy is administered by intravenous
infusion, reactions at the site of injection may occur: discomfort, itching,
burning, swelling or uninfected abscess. Cerezyme is available by prescription
only. For full prescribing information, please visit 

About Genzyme, a Sanofi Company

Genzyme has pioneered the development and delivery of transformative therapies
for patients affected by rare and debilitating diseases for over 30 years. We
accomplish our goals through world-class research and with the compassion and
commitment of our employees. With a focus on rare diseases and multiple
sclerosis, we are dedicated to making a positive impact on the lives of the
patients and families we serve. That goal guides and inspires us every day.
Genzyme`s portfolio of transformative therapies, which are marketed in countries
around the world, represents groundbreaking and life-saving advances in
medicine. As a Sanofi company, Genzyme benefits from the reach and resources of
one of the world`s largest pharmaceutical companies, with a shared commitment to
improving the lives of patients. Learn more at 

About Sanofi

Sanofi, a global and diversified healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients` needs. Sanofi has core
strengths in the field of healthcare with seven growth platforms: diabetes
solutions, human vaccines, innovative drugs, consumer healthcare, emerging
markets, animal health and the new Genzyme. Sanofi is listed in Paris (EURONEXT:
SAN) and in New York (NYSE: SNY). 

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