– 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 –
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 as immune thrombocytopenia and
anti-glomerular basement membrane disease. Monitor complete
blood counts with differential, serum creatinine levels, and
urinalysis with urine cell counts at periodic intervals for 48
months after the last dose of LEMTRADA.
LEMTRADA causes serious and life-threatening infusion
reactions. LEMTRADA must be administered in a setting with
appropriate equipment and personnel to manage anaphylaxis or
serious infusion reactions. Monitor patients for two hours
after each infusion. Make patients aware that serious infusion
reactions can also occur 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 skin exams.
Because of the risk of autoimmunity, infusion reactions, and
malignancies, LEMTRADA is available only through restricted
distribution under a Risk Evaluation and Mitigation Strategy
(REMS) Program. Call 1-855-676-6326 to enroll in 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
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Genzyme Media RelationsErin Pascal, +1
617-768-6864erin.pascal@genzyme.comorSanofi Media
RelationsJack Cox, +33 (0) 1 53 77 46
46mr@sanofi.comorSanofi Investor RelationsSébastien Martel,
+33 (0) 1 53 77 45 45ir@sanofi.com
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