Genzyme Announces Successful Phase III Results for Alemtuzumab (Lemtrada) in Multiple Sclerosis
-Significant efficacy of alemtuzumab over interferon
beta-1a (Rebif®) observed on both relapse and disability
co-primary endpoints in treatment-experienced MS patients -
- Genzyme confirms Q1 2012 regulatory submission objective
-
Paris, France - November 14,
2011 - Sanofi (EURONEXT: SAN
and NYSE: SNY) and its subsidiary
Genzyme report today that the
Phase lll CARE-MS ll trial met
both of its co-primary endpoints.
Relapse rate and sustained
accumulation (worsening) of disability
(SAD) were significantly reduced in
multiple sclerosis patients receiving
alemtuzumab (LEMTRADA™) as compared
with Rebif® (44 mcg subcutaneous
interferon beta-1a). Results
for both of these co-primary
endpoints were highly statistically
significant. CARE-MS II is
the randomized Phase III clinical trial comparing
the investigational drug alemtuzumab to interferon beta-1a in
patients with relapsing-remitting multiple
sclerosis (RRMS). Patients were
required to have experienced a
relapse while on a prior
therapy to be eligible for
CARE-MS II. Genzyme is
developing alemtuzumab in MS in collaboration with Bayer
HealthCare.
In this randomized trial involving 840 patients, a 49 percent
reduction in relapse rate was observed in patients treated with
alemtuzumab 12 mg compared to interferon beta-1a over two years of
study (p<0.0001). Importantly,
there was also a 42 percent
reduction in the risk of sustained
accumulation (worsening) of disability
as measured by the Expanded
Disability Status Scale (EDSS) (p=0.0084).
Analysis of the full CARE-MS II data is ongoing and results will be
presented at a forthcoming scientific meeting.
"CARE-MS ll represents the culmination of many years of clinical
and laboratory research aimed at demonstrating the
potential for alemtuzumab as a
highly effective treatment for MS and
understanding mechanisms involved in the complex natural history of
the disease," 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. "Taken together, the
Phase ll and lll clinical trial data illustrate the promise that
alemtuzumab holds
as a transformative treatment for people with relapsing MS."
The CARE-MS II trial compared
treatment with alemtuzumab 12 mg
given daily as an IV administration for 5
days, and then again for 3 days one year later, to treatment with
interferon beta-1a 44 mcg administered by injection three times per
week throughout the two years of study.
"The superior efficacy results for
alemtuzumab, particularly the slowing
of disability, are very promising since this was
a head-to-head comparison trial with high dose subcutaneous
interferon beta-1a," said Dr. Jeffrey
Cohen, Professor of Medicine
(Neurology), Cleveland Clinic Lerner College of
Medicine; Director of Experimental Therapeutics, Mellen Center for
MS Treatment and Research; and a member of the Steering Committee
overseeing the conduct of the study. “These
results suggest alemtuzumab's potential
to offer patients with MS a
new and effective treatment
option.”
The safety profile observed in the trial was consistent with
previous alemtuzumab use in MS and adverse events
continued to be manageable.
The most common types of
adverse events associated with alemtuzumab
in the CARE-MS II study were
infusion-associated reactions, the symptoms
of which most commonly included
headache, rash, nausea, hives, fever,
itching, insomnia, and fatigue.
Infections were common in both
groups with a higher incidence
in the alemtuzumab group. The
most common infections in patients
receiving alemtuzumab included upper
respiratory and urinary tract
infections, sinusitis and herpes
simplex infections. Infections were
predominantly mild to moderate in
severity and there were no
treatment-related life-threatening or fatal
infections.
Approximately 16 percent of
alemtuzumab-treated patients developed an
autoimmune thyroid-related adverse event and approximately
one percent developed immune thrombocytopenia during the
two-year study period. These
cases were detected early through
a monitoring program 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 MS.
“We are very pleased with
the results of the CARE-MS II
study which are unprecedented,” said
David Meeker, M.D.,
President and Chief
Executive Officer, Genzyme.
“We believe that
LEMTRADA™, with its impressive
efficacy, novel dosing regimen and
manageable safety profile,
could make a very important contribution to the MS treatment
landscape, where a significant unmet need still
exists for many patients.
Based on these positive results,
we are on track to submit
LEMTRADA™ for review to US and EU regulatory authorities in
the first quarter of 2012.”
Alemtuzumab has been granted Fast Track designation by the U.S.
Food and Drug Administration (FDA). The FDA's Fast Track
program is designed to expedite the review of new drugs that are
intended to treat serious or
life-threatening conditions and demonstrate
the potential to address unmet
medical needs. Under Fast Track
designation, alemtuzumab for MS is
eligible for Priority Review. 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 II Trial CARE-MS II (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 II was a
Phase III, global,
randomized clinical trial
comparing treatment with alemtuzumab to
treatment with subcutaneous interferon beta-1a (44 mcg administered
by injection three times per week) in 840 patients who relapsed
despite receiving prior MS treatment. Patients enrolled in
the trial had to have experienced at least two relapses within the
two years prior to entering the trial, with
at least one of these relapses
occurring within one year prior to
enrollment and at least one relapse occurring while on MS
therapy.
The CARE-MS II trial had two
co-primary endpoints: reduction in
relapse rate and six months sustained
accumulation of disability (SAD)**. 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. Disability assessments were
performed at regularly scheduled
visits by independent, evaluating
neurologists who were blinded to the patients’
treatment assignments. Relapse was determined by a blinded
committee.
**
Sustained Accumulation of Disability – Clinical
representation of the worsening of a patient’s level of
disability; CARE-MS ll 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 II study, another Phase III trial, CARE-MS I,
evaluated alemtuzumab against interferon beta-1a in
relapsing-remitting MS patients naive
to prior treatment and found a
statistically significant reduction in relapse
rate with alemtuzumab.
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, 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.
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.
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
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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
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commercially successful, the future approval and
commercial success of therapeutic
alternatives, the Group’s ability
to benefit from external growth
opportunities 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, 2010. Other than as required
by applicable law, Sanofi does not undertake any obligation to
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Genzyme® is a registered trademark and LEMTRADA™ is a
trademark of Genzyme Corporation. All rights reserved.
Rebif® is a registered trademark of EMD Serono, Inc. or
affiliates.
Contacts:
Genzyme Media Relations
Bo Piela
Tel: +1 617 768 6579
Mobile: +1 508 308 9783
E-mail: bo.piela@genzyme.com
Sanofi Media Relations Sanofi Investor Relations
Marisol Péron Sébastien Martel
Tel: +33 (0) 1 53 77 45 02 Tel: +33 (0) 1 53 77 45 45
E-mail: mr@sanofi.com E-mail: ir@sanofi.com
Posted: November 2011
