- Treatment with Genzyme’s Cerdelga® (eliglustat) for nine months
results in significant improvements in spleen volume, hemoglobin level,
liver volume and platelet count compared to placebo -
Company Website:
http://www.genzyme.com
CAMBRIDGE, Mass. -- (Business Wire)
Genzyme,
a Sanofi company, today announced the publication of results from the
ENGAGE registration study evaluating Cerdelga® (eliglustat) in
treatment-naïve patients with Gaucher disease type 1 in the February 17,
2015 issue
of The Journal of the American Medical Association.
The ENGAGE study is a Phase 3 randomized, double-blinded,
placebo-controlled, multinational registration trial of 40 eligible
treatment-naïve patients with Gaucher disease type 1 who had
splenomegaly in addition to thrombocytopenia and/or anemia at study
entry. Gaucher disease is a genetic disorder in which individuals fail
to produce glucocerebrosidase, an important enzyme that breaks down the
glycolipid glucocerebroside within lysosomes. In the absence of
glucocerebrosidase, lipids accumulate in the bone marrow, lungs, spleen,
liver and the brain – causing spleen and liver enlargement, red and
white blood cell abnormalities and bone deterioration; therefore
endpoints that specifically measured change in these symptoms were used
in the study.
Patients were stratified by baseline spleen volume and randomized 1:1 to
receive Cerdelga (50 or 100 mg twice daily) or placebo for nine months,
following assessment for improvements in disease manifestations.
According to the lead author Pramod Mistry, MD, PhD, FRCP, Professor of
Pediatrics & Internal Medicine at Yale University School of Medicine,
“We are very encouraged by these results as they ultimately point to a
safe and effective oral treatment option for patients living with
Gaucher disease.”
The primary efficacy endpoint of the study demonstrated:
-
A statistically significant reduction from baseline in spleen size by
a mean of 28 percent compared in Cerdelga patients with a mean
increase of two percent in placebo patients, for an absolute
difference of 30 percent (P<0.0001)
Secondary endpoints were also statistically significant:
-
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 6.6
percent compared with placebo (P=0.0072)
-
Platelet levels increased from baseline by an absolute difference of
41 percent compared with placebo (P<0.0001)
There were no serious adverse events associated with either treatment
group. All adverse reactions reported in the primary analysis period of
the ENGAGE study were mild or moderate and included arthralgia,
headache, migraine, flatulence, nausea, and oropharyngeal pain (all
occurring in greater than 10% of Cerdelga treated patients and more
frequently than placebo). One patient withdrew from the trial for a
reason not related to treatment. At the end of the nine months, patients
who were on placebo were transitioned to Cerdelga.
Genzyme developed Cerdelga, a first-line oral small molecule, to provide
a therapeutic alternative for individuals with Gaucher disease type 1
and expand the range of available treatment options for this rare
genetic disease. Cerdelga is a ceramide analog that works by blocking
the enzyme β-glucosylceramide synthase, slowing the production of
glucocerebroside, the substance that builds-up in patients’ lysosomes.
Patients with Gaucher disease type 1 retain some residual
glucocerebrosidase enzyme activity and Cerdelga aims to slow the
formation of the lipid to help balance the cell’s ability to clear it.
“We pioneered the world’s first therapy for Gaucher disease more than 20
years ago and have been dedicated ever since to advancing the science
behind Gaucher disease treatments,” said Genzyme’s Acting Head of Rare
Diseases, Richard Peters MD, Ph.D. “We remain committed to exploring
alternative and effective therapeutic approaches, like oral therapy,
that translate into meaningful outcomes for patients with unmet needs.”
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 Cerdelga®
Cerdelga® (eliglustat), 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, PhD, from the University of
Michigan. In pre-clinical studies, the molecule, developed with James A.
Shayman, MD, also from the University of Michigan, showed specificity
for glucosylceramide synthase. Following an extensive pre-clinical and
early clinical research program, Cerdelga® was studied in the largest
Phase 3 clinical program ever conducted in Gaucher disease, with
approximately 400 patients treated in 30 countries.
On August 19, 2014, the U.S. Food and Drug Administration (FDA) approved
Cerdelga® (eliglustat) capsules, the only first-line oral therapy for
certain adult Gaucher disease type 1 patients. The FDA approval was
based on efficacy data from two positive Phase 3 studies for Cerdelga®:
one in patients new to therapy (ENGAGE), and the other in patients
switching from approved enzyme replacement therapies (ENCORE). The
filing also incorporated four years of efficacy data from the Cerdelga®
Phase 2 study. On January 19, 2015, the European Commission (EC) also
granted marketing authorization for Cerdelga.
IMPORTANT SAFETY INFORMATION
Indications and Usage
Cerdelga® (eliglustat) capsules are indicated for the long-term
treatment of adults with Gaucher disease type 1 (GD1) who are CYP2D6
extensive metabolizers (EMs), intermediate metabolizers (IMs) or poor
metabolizers (PMs) as detected by an FDA-cleared test. Patients who are
CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate
concentrations of Cerdelga® to achieve a therapeutic effect. A specific
dose cannot be recommended for those patients whose CYP2D6 genotype
cannot be determined (indeterminate metabolizers).
Important Safety Information
Cerdelga® is contraindicated in the following patients due to the risk
of significantly increased Cerdelga® plasma concentrations which may
result in prolongation of the PR, QTc and/or QRS cardiac intervals that
could result in cardiac arrhythmias: EMs or IMs taking a strong or
moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A
inhibitor and IMs or PMs taking a strong CYP3A inhibitor.
Drugs that inhibit CYP2D6 and CYP3A may significantly increase the
exposure to Cerdelga®; Cerdelga® dose adjustment may be needed,
depending on metabolizer status. See section 7 of the full Prescribing
Information for more details and other potentially significant drug
interactions.
Because Cerdelga® is predicted to cause increases in ECG intervals at
substantially elevated plasma concentrations, use is not recommended in
patients with pre-existing cardiac disease, long QT syndrome, or in
combination with Class IA and Class III antiarrhythmic medications.
The most common adverse reactions (≥10%) for Cerdelga® are: fatigue,
headache, nausea, diarrhea, back pain, pain in extremities and upper
abdominal pain.
Only administer Cerdelga® during pregnancy if the potential benefit
justifies the potential risk; based on animal data, Cerdelga® may cause
fetal harm. Discontinue drug or nursing based on importance of drug to
mother. Cerdelga® is not recommended in patients with moderate to severe
renal impairment or in patients with hepatic impairment.
To report SUSPECTED ADVERSE REACTIONS, contact Genzyme Corporation at
(1-800-745-4447) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information, including patient Medication
Guide, for additional important safety information.
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 www.genzyme.com.
Genzyme® and Cerdelga® are registered trademarks
of Genzyme Corporation. All rights reserved.
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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the Private Securities Litigation Reform Act of 1995, as amended.
Forward-looking statements are statements that are not historical facts.
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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
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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,
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candidates as well as their decisions regarding labeling and other
matters that could affect the availability or commercial potential of
such product candidates, the absence of guarantee that the product
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approval and commercial success of therapeutic alternatives, the Group’s
ability to benefit from external growth opportunities, trends in
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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
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forward-looking information or statements.
Contacts:
Genzyme Media Contact:
Lori Gorski, 617-768-9344
lori.gorski@genzyme.com
or
Sanofi
Investor Relations Contact:
Sebastien Martel, +33 (0) 1.53.77.45.43
IR@sanofi.com
Source: Genzyme
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