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

PR Newswire/Les Echos/ 
 Genzyme Announces Positive New Data from Two Phase 3 Studies for Oral  
                Eliglustat Tartrate for Gaucher Disease 
Paris, France - February 15, 2013 - Sanofi (EURONEXT: SAN and NYSE: SNY) and 
its subsidiary Genzyme 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 nine 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(r)
(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 6 percent was observed in
the eliglustat tartrate arm compared with minus 3 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 &#8805;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 physician. 
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,
beta-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 program. 
Cerezyme Important Safety Information
Approximately 15 percent of patients have developed IgG antibodies to the
infused enzyme. 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, 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). 
Sanofi Forward Looking Statements
This press release contains forward-looking statements as defined in the Private
Securities Litigation Reform Act of 1995, as amended. Forward-looking statements
are statements that are not historical facts. These statements include
projections and estimates and their underlying assumptions, statements regarding
plans, objectives, intentions and expectations with respect to future financial
results, events, operations, services, product development and potential, and
statements regarding future performance. Forward-looking statements are
generally identified by the words "expects", "anticipates", "believes",
"intends", "estimates", "plans" and similar expressions. Although Sanofi's
management believes that the expectations reflected in such forward-looking
statements are reasonable, investors are cautioned that forward-looking
information and statements are subject to various risks and uncertainties, many
of which are difficult to predict and generally beyond the control of Sanofi,
that could cause actual results and developments to differ materially from those
expressed in, or implied or projected by, the forward-looking information and
statements. These risks and uncertainties include among other things, the
uncertainties inherent in research and development, future clinical data and
analysis, including post marketing, decisions by regulatory authorities, such as
the FDA or the EMA, regarding whether and when to approve any drug, device or
biological application that may be filed for any such product candidates as well
as their decisions regarding labelling and other matters that could affect the
availability or commercial potential of such product candidates, the absence of
guarantee that the product candidates if approved will be commercially
successful, the future approval and commercial success of therapeutic
alternatives, the Group's ability to benefit from external growth opportunities,
trends in exchange rates and prevailing interest rates, the impact of cost
containment policies and subsequent changes thereto, the average number of
shares outstanding as well as those discussed or identified in the public
filings with the SEC and the AMF made by Sanofi, including those listed under
"Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements"
in Sanofi's annual report on Form 20-F for the year ended December 31, 2011.
Other than as required by applicable law, Sanofi does not undertake any
obligation to update or revise any forward-looking information or statements. 
Genzyme(r) is a registered trademark. All rights reserved. 
Sanofi Media Relations                Sanofi Investor Relations
Marisol Péron                         Sébastien Martel
Tel: +33 (0) 1 53 77 46 46            Tel: +33 (0) 1 53 77 45 45
E-mail:                 E-mail:  
Genzyme Media Relations               Sanofi Investor Relations
Ingrid Mitchell                       Kristen Galfetti
Tel: (617) 768-6699                   Tel: +1 908 981 5560
E-mail:   E-mail: 
The content and accuracy of news releases published on this site and/or 
distributed by PR Newswire or its partners are the sole responsibility of the 
originating company or organisation. Whilst every effort is made to ensure the 
accuracy of our services, such releases are not actively monitored or reviewed 
by PR Newswire or its partners and under no circumstances shall PR Newswire or 
its partners be liable for any loss or damage resulting from the use of such 
information. All information should be checked prior to publication. 
-0- Feb/15/2013 17:25 GMT
Press spacebar to pause and continue. Press esc to stop.