Treatment with Genzyme’s Cerdelga®
(eliglustat) capsules maintains hematological and organ volume stability
in adults with Gaucher disease type 1 previously stabilized with
intravenous enzyme replacement therapy
Company Website:
http://www.genzyme.com
CAMBRIDGE, Mass. -- (Business Wire)
Genzyme,
a Sanofi company, today announced the publication of results from the
ENCORE study exploring Cerdelga® (eliglustat) as a
maintenance therapy suitable for adult patients who had reached
pre-specific treatment goals on enzyme replacement therapy (ERT) in the
March 26, 2015 online
issue of The Lancet.
ENCORE is a randomized, multinational, Phase 3, open-label,
non-inferiority study designed to determine whether patients with
Gaucher disease type 1 who had been stabilized after 3 or more years of
ERT infusions would remain stable after switching to Cerdelga, a novel,
oral, selective inhibitor of glucosylceramide synthase. Eligible
patients were randomized 2:1 to receive either oral Cerdelga (n=106) or
ERT with Cerezyme® (imiglucerase) (n=53) over a period of 12
months.
The composite primary efficacy endpoint was the percentage of patients
whose hematologic parameters and organ volumes remained stable, using
the following stability criteria established for patients with Gaucher
disease type 1 on maintenance therapy with Cerezyme:
-
Hemoglobin concentration that did not decrease more than 1.5 g/dL
-
Platelet count that did not decrease more than 25%
-
Spleen volume that did not increase more than 25%
-
Liver volume that did not increase more than 20%
After 12 months, 85% of patients receiving Cerdelga and 94% of patients
receiving Cerezyme met the composite endpoint of stability in all four
of these measures. The difference between the two treatments was within
the pre-specified margins.
The principal secondary endpoints were stability with respect to the
individual components of the primary endpoint. At least 93% of Cerdelga
patients remained stable with respect to hemoglobin concentration,
platelet count, spleen volume, and liver volume after 12 months of
treatment.
Additional endpoints evaluated bone disease, Gaucher disease severity,
quality-of-life and Gaucher-disease associated biomarkers. Baseline
values for these measures reflected the clinical stability of this
population, and no significant changes were seen after the switch to
Cerdelga, with the exception of decreases in levels of the plasma
biomarkers glucosylceramide and GM3. Given the mechanism of action of
Cerdelga®, these were expected and all values remained within the
healthy reference range.
A treatment preference survey done at the beginning of the trial found
that 94% of patients in both treatment groups had a preference for oral
treatment. After 12 months of treatment, all Cerdelga patients who
responded to the survey (94%) confirmed this treatment preference, with
the most frequent reasons cited being its convenience, capsule
formation, availability at home and feeling better after treatment.
Most adverse events were non-serious and mild or moderate in severity.
The most common side effects considered related to Cerdelga were
diarrhea (5% of patients), arthralgia (4%), fatigue (4%) and headache
(4%). Two Cerdelga patients and one Cerezyme patient (2% of each
treatment arm) discontinued treatment. Discontinuations in the Cerdelga
group were due to palpitations without clinically relevant ECG findings,
deemed possibly treatment-related and myocardial infarction, deemed
unrelated to treatment. The Cerezyme patient discontinued due to
psychotic disorder, deemed unrelated to treatment.
“These findings extend the efficacy profile of Cerdelga beyond
treatment-naïve adult patients with Gaucher disease type 1 to include
maintenance therapy in individuals who have been stabilized on enzyme
therapy,” said lead author Timothy M. Cox, Research Director & Professor
of Medicine at the University of Cambridge.
In Gaucher disease type 1, a deficiency of lysosomal acid β-glucosidase
leads to glucosylceramide accumulation in macrophages. This results in
symptoms including hepatosplenomegaly, anemia, thrombocytopenia and
skeletal disease.
Genzyme has been researching an oral therapy for Gaucher disease for 15
years, from early chemistry and preclinical research through clinical
development. Cerdelga is a ceramide analog that works by partially
inhibiting the enzyme UDP-glucosylceramide transferase, slowing the
production of β-glucosylceramide, the substance that builds up in the
lysosomes of affected patients. Patients with Gaucher disease type 1
retain residual acid β-glucosidase enzyme activity and Cerdelga aims to
reduce the rate at which the lipid is made so that the residual function
is able to clear the excess and re-establish a healthy equilibrium.
“These data suggest that Cerdelga is an effective, well-tolerated oral
therapy that will provide Gaucher disease type 1 patients with a
first-line treatment alternative to intravenous dosing,” said Genzyme’s
Acting Head of Rare Diseases, Richard Peters MD, PhD. “Since we
introduced the world’s first treatment for Gaucher disease type 1,
Genzyme has remained committed to patients with this disease. Survey
results indicate that many patients prefer an oral therapy and we are
proud to provide another treatment option to the Gaucher community.”
Genzyme’s clinical development program for Cerdelga was the largest
clinical program ever focused on Gaucher disease type 1 with
approximately 400 patients treated in 30 countries. Recently, results
from the ENGAGE study of Cerdelga in treatment-naïve patients were
published in TheJournal of the American Medical
Association.
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 that
breaks down a certain type of fat molecule (glucosylceramide). 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 proposed by the late Norman Radin,
PhD, from the University of Michigan. In pre-clinical studies, the
precursor molecule, developed with James A. Shayman, MD, also from the
University of Michigan, showed specificity for glucosylceramide
synthase. Following Genzyme’s extensive compound optimization,
pre-clinical and early clinical development 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.
The European Commission (EC) recently granted marketing authorization
for Cerdelga, based on data from its clinical development program.
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.
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
spleen).
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 www.genzyme.com.
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®, Cerdelga® and Cerezyme®
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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Contacts:
Genzyme Media Contact:
Lori Gorski, 617-768-9344
lori.gorski@genzyme.com
or
Sanofi
Investor Relations Contact:
Sebastien Martel, +33 (0) 1.53.77.45.45
IR@sanofi.com
Source: Genzyme
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