– In the extension of two Phase III pivotal studies, 68 and 60
percent of Lemtrada-treated patients received no additional Lemtrada in
the prior four years –
– Consistent effects seen across relapse, disability, brain
atrophy and MRI lesion activity –
Company Website:
http://www.genzyme.com
CAMBRIDGE, Mass. -- (Business Wire)
Genzyme,
a Sanofi
company, today announced positive new five-year investigational data
from the extension study of Lemtrada® (alemtuzumab) for
patients with relapsing remitting multiple sclerosis (RRMS). These
results will be presented on October 9, 2015 at the 31st
Congress of the European Committee for Treatment and Research in
Multiple Sclerosis (ECTRIMS) in Barcelona, Spain.
In RRMS patients treated with Lemtrada in the Phase III pivotal studies,
the effects described below observed in the two-year trials were
maintained through three additional years in the extension study (years
three, four and five). After the initial two courses of treatment in the
pivotal studies, which were given at month zero and at month 12, 68
percent of Lemtrada patients from CARE-MS I and 60 percent from CARE-MS
II did not receive additional Lemtrada treatment during the following
four years, through month 60.
-
The low annualized relapse rates observed in patients who received
Lemtrada in CARE-MS I (0.18) and CARE-MS II (0.27) were maintained
from year three (0.19 and 0.22) to year five (0.15 and 0.18).
-
Through year five, 80 percent and 76 percent of patients who received
Lemtrada in CARE-MS I and CARE-MS II, respectively, did not experience
worsening of disability progression confirmed over six months as
measured by the Expanded Disability Status Scale (EDSS).
-
Through year five, 33 percent and 43 percent of patients who had some
disability before receiving Lemtrada in CARE-MS I and CARE-MS II,
respectively, had improvement in EDSS score confirmed over at least
six months as compared with pre-treatment baseline.
-
Through year five, patients who received Lemtrada in CARE-MS I and II
experienced a slowing of brain atrophy as measured by brain
parenchymal fraction on magnetic resonance imaging (MRI). In years
three, four and five, the median yearly brain volume loss was -0.20
percent or less, which was lower than what was observed during the
two-year pivotal studies.
-
In each of years three, four and five, most patients had no evidence
of MRI disease activity (70 – 72 percent, CARE-MS I; 68 – 70 percent,
CARE-MS II.)
Through year five, the incidence of most adverse events during the
extension study was comparable or reduced compared with the pivotal
studies. The frequency of thyroid adverse events was highest in year
three and declined thereafter.
The Phase III trials of Lemtrada were randomized, rater-blinded,
two-year pivotal studies comparing treatment with Lemtrada to high-dose
subcutaneous interferon beta-1a (Rebif®) in patients with
RRMS who had active disease and were either new to treatment (CARE-MS I)
or who had an inadequate response to another therapy (CARE-MS II).
More than 90 percent of the patients who were treated with Lemtrada in
the CARE-MS Phase III trials enrolled in the extension study. These
patients were eligible to receive additional treatment with Lemtrada in
the extension study if they experienced at least one relapse or at least
two new or enlarging brain or spinal cord lesions.
“These data illustrate that most Lemtrada patients experienced
sustained effects of treatment, despite the absence of additional
treatment courses,” said Professor Eva Havrdová, MD, PhD, MS Center,
Department of Neurology, First Medical Faculty, Charles University,
Prague, Czech Republic. "It is encouraging to see consistent
effects maintained across multiple meaningful outcomes through five years.”
In clinical trials, serious side effects associated with Lemtrada
included infusion-associated reactions, autoimmune disorders (such as
thyroid disease, autoimmune cytopenias, and nephropathies), infections
and pneumonitis. Risk management programs incorporating education and
monitoring help support early detection and management of key identified
and potential risks. The most common side effects of Lemtrada are rash,
headache, pyrexia, nasopharyngitis, nausea, urinary tract infection,
fatigue, insomnia, upper respiratory tract infection, herpes viral
infection, urticaria, pruritus, thyroid gland disorders, fungal
infection, arthralgia, pain in extremity, back pain, diarrhea,
sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain,
flushing, and vomiting. (See Important Safety Information below.)
“The five-year data announced today are exciting and important for
people living with relapsing MS, because of Lemtrada’s potential to
change the treatment approach for patients who continue to suffer from
this debilitating disease, and for whom Lemtrada is an option,” said
Bill Sibold, Head of Genzyme’s Multiple Sclerosis business.
In CARE-MS I, Lemtrada was significantly more effective than interferon
beta-1a at reducing annualized relapse rates; the difference observed in
slowing disability progression did not reach statistical significance.
In CARE-MS II, Lemtrada was significantly more effective than interferon
beta-1a at reducing annualized relapse rates, and accumulation of
disability was significantly slowed in patients given Lemtrada vs.
interferon beta-1a.
Lemtrada® (alemtuzumab) U.S. Indication
LEMTRADA is indicated for the treatment of patients with relapsing forms
of multiple sclerosis (MS). Because of its safety profile, the use of
LEMTRADA should generally be reserved for patients who have had an
inadequate response to two or more drugs indicated for the treatment of
MS.
CONTRAINDICATIONS
LEMTRADA is contraindicated in patients who are infected with Human
Immunodeficiency Virus (HIV) because LEMTRADA causes prolonged
reductions of CD4+ lymphocyte counts.
Important Safety Information About Lemtrada
WARNING: AUTOIMMUNITY, INFUSION REACTIONS, AND MALIGNANCIES
LEMTRADA causes serious, sometimes fatal, autoimmune conditions such
asimmune thrombocytopenia and anti-glomerular basement membrane
disease.Monitor complete blood counts with differential, serum
creatinine levels, andurinalysis with urine cell counts at
periodic intervals for 48 months after the last doseof LEMTRADA.
LEMTRADA causes serious and life-threatening infusion reactions.
LEMTRADAmust be administered in a setting with appropriate
equipment and personnel tomanage anaphylaxis or serious infusion
reactions. Monitor patients for two hoursafter each infusion.
Make patients aware that serious infusion reactions can alsooccur
after the 2-hour monitoring period.
LEMTRADA may cause an increased risk of malignancies, including
thyroid cancer,melanoma, and lymphoproliferative disorders.
Perform baseline and yearly skinexams.
Because of the risk of autoimmunity, infusion reactions, and
malignancies,LEMTRADA is available only through restricted
distribution under a RiskEvaluation and Mitigation Strategy
(REMS) Program. Call 1-855-676-6326 to enrollin the LEMTRADA
REMS Program.
WARNINGS AND PRECAUTIONS
Autoimmunity: Treatment with LEMTRADA can result in the formation
of autoantibodies and increase the risk of serious autoimmune mediated
conditions, and may increase the risk of other autoimmune conditions
because of the broad range of autoantibody formation. Obtain complete
blood counts (CBC) with differential, serum creatinine levels, and
urinalysis with cell counts before starting treatment and then at
monthly intervals for 48 months after the last dose of LEMTRADA, or
longer, if clinically indicated.
Infusion Reactions: LEMTRADA causes cytokine release syndrome
resulting in infusion reactions. In clinical studies, 92% of
LEMTRADA-treated patients experienced infusion reactions. Serious
reactions occurred in 3% of these patients and included anaphylaxis in 2
patients (including anaphylactic shock), angioedema, bronchospasm,
hypotension, chest pain, bradycardia, tachycardia (including atrial
fibrillation), transient neurologic symptoms, hypertension, headache,
pyrexia, and rash. In some patients, infusion reactions were reported
more than 24 hours after LEMTRADA infusion. Premedicate patients with
corticosteroids immediately prior to LEMTRADA infusion for the first 3
days of each treatment course. Consider pretreatment with antihistamines
and/or antipyretics. Infusion reactions may occur despite pretreatment.
Malignancies: Monitor for symptoms of thyroid cancer. Because
LEMTRADA is an immunomodulatory therapy, caution should be exercised in
initiating LEMTRADA in patients with pre-existing or ongoing
malignancies.
LEMTRADA REMS Program: Only prescribers, patients, pharmacies and
healthcare facilities certified and enrolled in the REMS program can
prescribe, receive, dispense or administer LEMTRADA. Healthcare
facilities must have on-site access to equipment and personnel trained
to manage infusion reactions (including anaphylaxis and cardiac and
respiratory emergencies).
Immune thrombocytopenia (ITP) occurred in 2% of LEMTRADA-treated
patients in clinical studies in MS. One LEMTRADA-treated patient
developed ITP that went unrecognized prior to the implementation of
monthly monitoring requirements, and died from an intracerebral
hemorrhage. ITP has been diagnosed more than 3 years after the last
LEMTRADA dose. If ITP is confirmed, promptly initiate medical
intervention.
Glomerular nephropathies occurred in 0.3% of LEMTRADA-treated
patients in MS clinical trials and have been diagnosed up to 40 months
after the last dose of LEMTRADA. Anti-glomerular basement membrane
(anti-GBM disease) can lead to renal failure requiring dialysis and
transplantation and has in post-marketing cases of MS patients treated
with alemtuzumab. Anti-GBM disease can be life-threatening if untreated;
early detection and treatment may decrease the risk of poor outcomes.
Autoimmune thyroid disorders occurred in 34% of LEMTRADA-treated
patients in clinical studies. Newly diagnosed thyroid disorders occurred
throughout the uncontrolled clinical study follow-up period, more than 7
years after the first LEMTRADA dose. Serious thyroid events occurred in
2% of patients, including cardiac and psychiatric events. In
LEMTRADA-treated patients, 3% underwent thyroidectomy. In patients with
an ongoing thyroid disorder, LEMTRADA should be administered only if the
potential benefit justifies the potential risks. Obtain thyroid function
tests prior to initiation of treatment and every 3 months until 48
months after the last infusion, or longer, if clinically indicated.
Thyroid disease poses special risks in women who are pregnant.
Autoimmune cytopenias occurred in LEMTRADA-treated MS patients in
clinical trials. One LEMTRADA-treated patient with autoimmune
pancytopenia died from sepsis. Prompt medical intervention is indicated
if a cytopenia is confirmed.
Infections occurred in 71% of LEMTRADA-treated patients compared
to 53% of patients treated with interferon beta-1a. Serious infections
occurred in 3% of patients treated with LEMTRADA and 1% of patients
treated with interferon beta-1a and included: appendicitis,
gastroenteritis, pneumonia, herpes zoster, and tooth infection. Consider
delaying LEMTRADA administration in patients with active infection until
the infection is fully controlled.
-
Do not administer live viral vaccines following a course of LEMTRADA,
as patients may be at increased risk of infection.
-
Concomitant use of antineoplastic or immunosuppressive therapies could
increase the risk of immunosuppression.
-
Herpes viral infection developed in 16% of LEMTRADA-treated patients
compared to 3% of interferon beta-1a patients. Administer antiviral
prophylaxis for herpetic viral infections starting on the first day of
each treatment course and continue for a minimum of two months
following treatment with LEMTRADA or until CD4+ lymphocyte count is
≥200 cells per microliter, whichever occurs later.
-
Cervical human papilloma virus (HPV) infection occurred in 2% of
LEMTRADA treated patients. Annual screening is recommended for female
patients.
-
Active and latent tuberculosis cases occurred in 0.3% of
LEMTRADA-treated patients, most often in endemic regions.
-
Fungal infections, especially oral and vaginal candidiasis, occurred
in 12% of LEMTRADA-treated patients compared to 3% of interferon
beta-1a patients.
-
Cases of listeria meningitis occurred within 1 month of LEMTRADA
dosing. Advise patients to avoid or adequately heat foods that are
potential sources for Listeria monocytogenes.
-
Before initiating LEMTRADA, consider screening patients at high risk
of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection.
Carriers of HBV and/or HCV who receive LEMTRADA may be at risk of
irreversible liver damage relative to a potential virus reactivation.
Pneumonitis, including hypersensitivity pneumonitis and
pneumonitis with fibrosis, occurred in 6 of 1217 (0.5%) LEMTRADA-treated
patients in clinical studies. Advise patients to report symptoms of
pneumonitis (e.g., shortness of breath, cough, wheezing, chest pain or
tightness, and hemoptysis).
Drug Products with Same Active Ingredient: LEMTRADA contains the
same active ingredient (alemtuzumab) found in CAMPATH®. If LEMTRADA is
considered for use in a patient who has previously received CAMPATH,
exercise increased vigilance for additive and long-lasting effects on
the immune system.
Adverse Reactions
In clinical trials, the most common adverse reactions (incidence ≥10%
and >interferon beta-1a) with LEMTRADA vs interferon beta-1a were: rash
(53% vs 6%), headache (52% vs 23%), pyrexia (29% vs 9%), nasopharyngitis
(25% vs 19%), nausea (21% vs 9%), urinary tract infection (19% vs 8%),
fatigue (18% vs 13%), insomnia (16% vs 15%), upper respiratory tract
infection (16% vs 13%), herpes viral infection (16% vs 3%), urticaria
(16% vs 2%), pruritus (14% vs 2%), thyroid gland disorders (13% vs 3%),
fungal infection (13% vs 4%), arthralgia (12% vs 9%), pain in extremity
(12% vs 9%), back pain (12% vs 8%), diarrhea (12% vs 6%), sinusitis (11%
vs 8%), oropharyngeal pain (11% vs 5%), paresthesia (10% vs 8%),
dizziness (10% vs 5%), abdominal pain (10% vs 5%), flushing (10% vs 4%),
and vomiting (10% vs 3%).
Use in Specific Populations
LEMTRADA should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. Autoantibodies may be
transferred from the mother to the fetus during pregnancy. Placental
transfer of anti-thyroid antibodies resulted in a case of neonatal
Graves’ disease. Safety and effectiveness in pediatric patients less
than 17 years of age have not been established. Use of LEMTRADA is not
recommended in pediatric patients due to the risks of autoimmunity and
infusion reactions, and because it may increase the risk of malignancies.
Please click here
for full US Prescribing Information for Lemtrada, including Boxed WARNING.
About Lemtrada® (alemtuzumab)
Lemtrada is approved in more than 40 countries, with additional
marketing applications under review. Lemtrada is supported by a
comprehensive and extensive clinical development program that involved
nearly 1,500 patients worldwide and 5,400 patient-years of follow-up.
Alemtuzumab is a monoclonal antibody that targets CD52, a protein
abundant on T and B cells. Circulating T and B cells are thought to be
responsible for the damaging inflammatory process in MS. Although the
exact mechanism of action for alemtuzumab is unknown, it is presumed to
deplete circulating T and B lymphocytes after each treatment course.
Lymphocyte counts then increase over time with a reconstitution of the
lymphocyte population that varies for the different lymphocyte subtypes.
Genzyme holds the worldwide rights to alemtuzumab and has responsibility
for its development and commercialization in multiple sclerosis. Bayer
Healthcare receives contingent payments based on global sales revenue.
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 Lemtrada® are registered
trademarks of Genzyme Corporation. Rebif® is a
registered trademark of EMD Serono, Inc. 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 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.
View source version on businesswire.com: http://www.businesswire.com/news/home/20151007006545/en/
Contacts:
Genzyme Media Relations
Erin Pascal, +1 617-768-6864
erin.pascal@genzyme.com
or
Sanofi
Media Relations
Jack Cox, +33 (0) 1 53 77 46 46
mr@sanofi.com
or
Sanofi
Investor Relations
Sébastien Martel, +33 (0) 1 53 77 45 45
ir@sanofi.com
Source: Genzyme Corporation
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