CAMBRIDGE, Mass.--(BUSINESS WIRE)--Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme
announced today new results from the CARE-MS I trial, the first of two
randomized, Phase III clinical trials comparing the investigational drug
alemtuzumab (Lemtrada™) to Rebif® (high dose
subcutaneous interferon beta-1a) in patients with relapsing-remitting
multiple sclerosis (MS). New data show that 78 percent of patients
treated with alemtuzumab remained relapse-free for two years, providing
statistically significant improvement over interferon beta-1a (78
percent vs 59 percent at two years, p<0.0001) and meeting this secondary
endpoint. The CARE-MS I results were presented today at the 5th
Joint Triennial Congress of the European and Americas Committees for
Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS). Genzyme
is developing alemtuzumab for relapsing MS in collaboration with Bayer
HealthCare.
“We look forward to
the results of CARE-MS II, our second Phase III study, later this year
to extend these results by confirming Lemtrada’s effects in patients
with continued disease activity while receiving another MS treatment.”
As previously reported, treatment with alemtuzumab resulted in a 55
percent reduction in relapse rate compared to interferon beta-1a over
two years of study (p<0.0001), satisfying this co-primary endpoint and
meeting the predefined protocol criteria for declaring the study a
success. At the two-year time point, very few alemtuzumab patients (8
percent) experienced a sustained increase, or worsening, in disability
as measured by the Expanded Disability Status Scale (EDSS) (vs 11
percent of patients in the interferon beta-1a group). However, the
difference between groups for this co-primary endpoint was not
statistically significant (p=0.22) and there was no difference in the
mean EDSS score between groups.
The CARE-MS I trial compared treatment with alemtuzumab (12 mg/day by IV
administration for 5-days, with a second 3-day IV administration one
year later), to treatment with subcutaneous interferon beta-1a (44 mcg
administered by injection three times per week) in 581 patients with
relapsing-remitting MS who had received no previous treatment to
suppress MS, except for steroids.
“CARE-MS I confirms that, in a head-to-head comparison with Rebif,
disease activity is significantly reduced in patients with early
relapsing-remitting multiple sclerosis treated with alemtuzumab, over
the first two years of observation,” said Professor Alastair
Compston, Chair of the Steering Committee overseeing the conduct of the
study and head of the Department of Clinical Neurosciences at the
University of Cambridge, United Kingdom. “These data support the
robust efficacy profile and potential that alemtuzumab offers for
patients with relapsing-remitting multiple sclerosis requiring a more
effective option than currently available therapies.”
“Lemtrada’s robust effects over and above those of Rebif on relapses
and a variety of clinical and imaging endpoints reinforces its potential
as an effective treatment option for MS patients,” said David
Meeker, M.D., Chief Operating Officer, Genzyme. “We look forward to
the results of CARE-MS II, our second Phase III study, later this year
to extend these results by confirming Lemtrada’s effects in patients
with continued disease activity while receiving another MS treatment.”
Additional findings from the CARE-MS I study presented today include
other secondary endpoints that suggest positive outcomes with
alemtuzumab. Improvement in Multiple Sclerosis Functional Composite
(MSFC) scores was observed in alemtuzumab-treated patients, as compared
to interferon beta-1a (0.12 vs 0.05 mean change from baseline at year
two, p=0.012). MSFC is a composite measurement of physical and cognitive
function.
The effect of alemtuzumab on reduction in T2-hyperintense lesion volume
compared to interferon beta-1a was -9.3 vs -6.5 median percent change at
year two (p=0.31). Other MRI outcomes suggested that alemtuzumab
provided improvement over interferon beta-1a across a number of
image-related endpoints, generally consistent with the effects observed
in the clinical endpoints. Statistically significant improvement was
observed for alemtuzumab over interferon beta-1a in the percentage of
patients with new and enlarging T2-hyperintense lesions (49 vs 58,
p=0.035); with new gadolinium-enhancing lesions (15 vs 27, p=0.0006);
and with new T1-hypointense lesions (24 vs 31, p=0.05). In addition,
alemtuzumab-treated patients experienced less change in brain
parenchymal fraction (BPF), a measure of brain atrophy, compared to
interferon beta-1a (-0.87 vs -1.49 median percent change from baseline,
p<0.0001), a highly statistically significant result.
CARE-MS I Safety Findings
Common adverse events associated with alemtuzumab in the CARE-MS I study
included infusion-associated reactions which were generally mild to
moderate. Additionally, the incidence of infections was increased, the
most common infections involving the upper respiratory and urinary tract
and oral herpes. Infections were predominantly mild to moderate in
severity and none were life-threatening or fatal.
The incidence of serious adverse events was similar between the two
treatment arms (18.4 percent for alemtuzumab vs 14.4 percent for
interferon beta-1a). Relating to autoimmune disorders, 18.1 percent of
alemtuzumab-treated patients developed an autoimmune thyroid-related
adverse event and 0.8 percent developed immune thrombocytopenia (ITP)
during the two-year study period. There were no cases of anti-GBM
disease. Cases of autoimmunity were detected and managed using
conventional therapies. Patient monitoring for immune cytopenias and
thyroid or renal disorders is incorporated in all Genzyme-sponsored
trials of alemtuzumab for the investigational treatment of multiple
sclerosis.
Additional Information
Another Phase III clinical trial, CARE-MS II, is currently underway,
evaluating alemtuzumab against interferon beta-1a in relapsing-remitting
MS patients who have relapsed while on therapy. Top-line results from
that trial are expected to be available in the fourth quarter of 2011.
The company expects to file for U.S. and E.U. approval of alemtuzumab in
relapsing MS in the first quarter of 2012, and alemtuzumab has been
granted Fast Track designation by the U.S. Food and Drug Administration
(FDA). Since it is not yet approved for the treatment of MS, alemtuzumab
must not be used in MS patients outside of a formal, regulated clinical
trial setting in which appropriate patient monitoring measures are in
place.
*Lemtrada™ is the proprietary name submitted to health
authorities for the company’s investigational multiple sclerosis agent
alemtuzumab.
About the CARE-MS I Trial
CARE-MS I (The Comparison of alemtuzumab and Rebif® Efficacy
in Multiple Sclerosis) trial was designed to evaluate whether the
investigational MS therapy alemtuzumab could achieve meaningful efficacy
and safety improvements over the approved, active comparator interferon
beta-1a, a standard treatment for relapsing MS.
CARE-MS I was a Phase III, global, randomized clinical trial comparing
treatment with alemtuzumab (12 mg/day for a 5-day IV administration,
with a second 3-day IV administration one year later), to treatment with
subcutaneous interferon beta-1a (44 mcg administered by injection three
times per week) in 581 patients with relapsing-remitting MS who had
received no previous treatment to suppress MS, except for steroids.
Patients were randomized at a ratio of 2 to 1 to receive alemtuzumab or
interferon beta-1a. Co-primary efficacy endpoint assessments were
performed at regularly scheduled visits by independent, evaluating
neurologists who were blinded to the patients’ treatment assignments.
The CARE-MS I trial had co-primary endpoints: reduction in relapse rate
and six months sustained accumulation of disability (SAD) †.
Based on the criteria set forth in the study protocol, CARE-MS I is
defined as a success if both co-primary endpoints are met (p≤0.05) or if
one co-primary endpoint is met against a more stringent measure of
statistical significance (p≤0.025). Secondary outcome measures include:
Percentage of relapse-free patients at year two; Expanded Disability
Status Scale (EDSS) change from baseline; percent change in
magnetic/resonance imaging (MRI)-T2-hyperintense lesion volume at year
two; and Multiple Sclerosis Functional Composite (MSFC) change from
baseline.
†Sustained Accumulation of Disability (SAD) – Clinical
representation of the worsening of a patient’s level of disability;
CARE-MS 1 monitored this endpoint over the course of six months.
About Alemtuzumab
Alemtuzumab is a humanized monoclonal antibody being studied as a
potential therapy for relapsing MS. Alemtuzumab targets the cell-surface
glycoprotein CD52, which is highly expressed on T- and B-lymphocytes.
Preliminary research suggests that alemtuzumab initially depletes the T-
and B-cells that may be responsible for the cellular damage in MS. This
depletion of T- and B-cells is followed by a distinctive pattern of
lymphocyte repopulation. Alemtuzumab appears to have little or no effect
on other cells of the immune system. In addition to the completed
CARE-MS I study, another Phase III trial, CARE-MS II, will evaluate
alemtuzumab against interferon beta-1a in relapsing-remitting MS
patients who have relapsed while on therapy.
Genzyme has the worldwide rights to alemtuzumab and has primary
responsibility for the development and commercialization of alemtuzumab
in MS. Bayer HealthCare has been co-developing alemtuzumab in MS with
Genzyme. Bayer HealthCare retains an option to co-promote alemtuzumab in
MS and upon regulatory approval and commercialization would receive
contingent payments based on sales revenue.
About Genzyme
One of the world’s leading biotechnology companies, Genzyme is dedicated
to making a major positive impact on the lives of people with serious
diseases. Since its founding in 1981, the company has introduced
breakthrough treatments that have provided new hope for patients in the
fields of rare inherited disorders, kidney disease, orthopaedics,
cancer, transplant, and immune diseases. Genzyme is a Sanofi company.
Genzyme’s press releases and other company information are available at www.genzyme.com.
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, rare
diseases, consumer healthcare, emerging markets and animal health.
Sanofi is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the
fields of health care, nutrition and high-tech materials. Bayer
HealthCare, a subgroup of Bayer AG with annual sales of more than EUR
16.913 billion (2010), is one of the world’s leading, innovative
companies in the healthcare and medical products industry and is based
in Leverkusen, Germany. The company combines the global activities of
the Animal Health, Consumer Care, Medical Care and Pharmaceuticals
divisions. Bayer HealthCare’s aim is to discover and manufacture
products that will improve human and animal health worldwide. Bayer
HealthCare has a global workforce of 55.700 employees and is represented
in more than 100 countries. Find more information at www.bayerhealthcare.com.
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