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
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 The Journal of the American Medical
Association.
About Gaucher diseaseGaucher 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 UsageCerdelga (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 InformationCerdelga 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 InformationCerezyme
(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 CompanyGenzyme 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 SanofiSanofi, 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, 2014. Other
than as required by applicable law, Sanofi does not undertake any
obligation to update or revise any forward-looking information or
statements.
Genzyme Media Contact:Lori Gorski,
617-768-9344lori.gorski@genzyme.comorSanofi Investor Relations
Contact:Sebastien Martel, +33 (0) 1.53.77.45.45IR@sanofi.com
Banco Santander (NYSE:SAN)
Historical Stock Chart
From Apr 2024 to May 2024
Banco Santander (NYSE:SAN)
Historical Stock Chart
From May 2023 to May 2024