Trials Demonstrate Long-term Efficacy, Safety and Tolerability of
Oral Therapy to Treat Certain Adults with Gaucher Disease Type 1
Company Website:
http://www.genzyme.com
CAMBRIDGE, Mass. -- (Business Wire)
Genzyme,
a Sanofi company, today reported extension study data from its Phase 3
ENGAGE and ENCORE studies of Cerdelga® (eliglustat), a
first-line oral therapy approved by the FDA and the European Commission
for the treatment of certain adults with Gaucher disease type 1. The
results from the studies were presented today at the 11th
Annual Lysosomal Disease Network WORLD Symposium in Orlando, Fla. Both
extension studies demonstrated continued stability and/or improvements
across established end points and published therapeutic treatment goals.
Genzyme developed Cerdelga, a capsule taken orally, to provide a
treatment alternative for certain adult 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 Cerdelga
represents the largest clinical program ever focused on Gaucher disease,
with approximately 400 patients treated in 29 countries.
The oral presentations on these Phase 3 studies were:
-
ENGAGE — A Phase 3, Randomized, Double-Blind, Placebo-Controlled,
Multi-Center Study to Investigate the Efficacy and Safety of
Eliglustat in Adults with Gaucher Disease Type 1: Results after 18
Months, Pramod Mistry, MBBS, PhD, F.R.C.P, Director of Yale Lysosomal
Disease Center and Gaucher Disease Treatment Center Yale School of
Medicine: In the primary analysis period, improvements were seen
across the following endpoints after 9 months on Cerdelga: spleen
size, platelet count, hemoglobin concentration, and liver volume. In
the 9 month extension phase, patients who switched from placebo to
eliglustat showed improvements similar to the eliglustat-treated
patients during the primary analysis while the eliglustat-treated
patients continued to show improvements during the 9 month extension
period. There were no treatment-related discontinuations.
-
ENCORE— a Phase 3, Randomized, Controlled, Open-Label Non-Inferiority
Study Comparing Eliglustat to Imiglucerase in Gaucher Disease Type 1
Patients Stabilized on Enzyme Replacement Therapy: 24-Month Results,
Timothy M. Cox, MD, FRCP, Research Director and Professor of Medicine,
Addenbrooke’s Hospital, Cambridge, UK. The study, which met the
primary analysis criteria for non-inferiority to imiglucerase (Cerezyme®),
had a composite endpoint of each of the following parameters: spleen
volume, hemoglobin concentration, platelet counts, and liver volume at
12 months. During the 12-month extension period, the patients who
crossed over to eliglustat treatment from imiglucerase remained
stable. Patients treated with eliglustat for 24 months also maintained
stability of clinical parameters during the extension period.
The most common adverse reactions (≥10%) in the primary analysis periods
of ENGAGE and ENCORE were fatigue, headache, nausea, diarrhea, back
pain, pain in extremities, and upper abdominal pain. In both extension
studies the majority of adverse reactions with Cerdelga were mild and
transient, and consistent with those in the primary analysis periods.
Most patients in both of the Phase 3 studies continue to receive
Cerdelga in longer term extension periods. The majority of patients are
now in their 4th or 5th year of treatment.
“The continued work within Genzyme’s Gaucher program and the approval of
Cerdelga represent are important to both the company and this patient
community,” said Genzyme’s Acting Head of Rare Diseases, Richard Peters,
M.D., Ph.D. “The results of the extension studies in which the majority
of patients stayed on therapy support the use of Cerdelga as a
first-line treatment option for the long-term management of Gaucher
disease type 1.”
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 the
enzyme, β-glucosidase (glucocerebrosidase) leading to the accumulation
of its substrate, 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
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.
Cerdelga is registered as an orphan medicinal product for the treatment
of Gaucher disease in the Community Register of Orphan Medicinal
Products.
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
Approximately 15% of patients have developed IgG antibodies to Cerezyme
during the first year of therapy. Approximately 46% of patients with
detectable IgG antibodies experienced symptoms of hypersensitivity, and
these patients have a higher risk of hypersensitivity. It is suggested
that patients be monitored periodically for IgG antibody formation
during the first year of treatment.
Hypersensitivity has also been observed in patients without detectable
IgG antibodies. Symptoms suggestive of hypersensitivity have been noted
in approximately 6.6% of all patients, and anaphylactoid reactions in
less than 1%. Treatment with Cerezyme should be approached with caution
in patients who have exhibited hypersensitivity symptoms such as
pruritus, flushing, urticarial, angioedema, chest discomfort, dyspnea,
coughing, cyanosis, and hypotension. Pre-treatment with antihistamines
and/or corticosteroids and a reduced rate of infusion may allow
continued treatment in most patients.
In less than 1% of patients, pulmonary hypertension and pneumonia have
been observed during treatment with Cerezyme. These are known
complications of Gaucher disease regardless of treatment. Patients with
respiratory symptoms in the absence of fever should be evaluated for the
presence of pulmonary hypertension.
Approximately 13.8% of patients have experienced adverse events related
to treatment with Cerezyme. Some of these are injection site reactions
such as discomfort, pruritus, burning, swelling or sterile abscess at
the site at the site of venipuncture. Additional adverse reactions that
have been reported include nausea, abdominal pain, vomiting, diarrhea,
rash, fatigue, headache, fever, dizziness, chills, backache, and
tachycardia. Transient peripheral edema has also been reported for this
therapeutic class of drug.
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®, Cerezyme®, and Cerdelga® are
registered trademarks of Genzyme Corporation. All rights reserved.
About Sanofi
Sanofi, a global 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 Genzyme. Sanofi is
listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
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, 2013. Other than as required by applicable
law, Sanofi does not undertake any obligation to update or revise any
forward-looking information or statements.
Contacts:
Media Contact:
Genzyme
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
© 2024 Canjex Publishing Ltd. All rights reserved.