CAMBRIDGE, Mass.--(BUSINESS WIRE)--Genzyme
Corp., a subsidiary of sanofi-aventis Group (EURONEXT: SAN and NYSE:
SNY), today reported additional five-year patient data from its
completed Phase 2 multiple sclerosis (MS) trial showing that nearly
two-thirds of alemtuzumab treated patients remained free of
clinically-active disease as much as four years after most patients
received their last course of the investigational drug. The data were
presented at the American Academy of Neurology's 63rd Annual Meeting.
“The improvements seen with alemtuzumab treatment as
compared with interferon beta are encouraging.”
The CAMMS223 Phase 2 trial, first reported in the New England Journal
of Medicine in 2008, compared alemtuzumab to the approved MS therapy
Rebif® (high dose interferon beta-1a) in early, active,
relapsing-remitting multiple sclerosis (RRMS) patients who had received
no prior therapy. In the trial, alemtuzumab was given to patients in two
or three annual cycles of not more than five days per cycle, while Rebif
was given to patients three times per week, every week for three years.
The study included an extended phase for collection of long-term
efficacy and safety data.
Results of the five-year review showed:
an estimated 65 percent of alemtuzumab-treated patients were free of
clinically-active disease, compared to 27 percent of patients taking
Rebif (p<0.0001). To be free of clinically-active disease, MS patients
in the trial were both relapse-free and without a sustained increase
in disability as measured by the Expanded Disability Status Scale
(EDSS) through five years;
an estimated 72 percent of alemtuzumab-treated patients were
relapse-free compared to 41 percent of patients taking Rebif; and
an estimated 87 percent of alemtuzumab-treated patients were free of
sustained accumulation of disability compared to 62 percent of
patients taking Rebif (previously reported).
“These data suggest that alemtuzumab may have great potential for MS
patients,” said abstract author Cary Twyman, MD, principal Investigator,
Associates in Neurology, Lexington, KY.
Two pivotal Phase 3 studies investigating alemtuzumab, CARE-MS I and II,
are currently ongoing. Top-line results from these trials are expected
to be available respectively early in the third quarter of 2011 and in
the fourth quarter of 2011. The company expects to file for U.S. and
E.U. approval in early 2012, and has been granted fast track status by
the FDA for this submission.
Alemtuzumab Seen to Improve Low-Contrast Vision
Visual impairment is a common complication of multiple sclerosis. A
second abstract presented at AAN reported that sustained improvement in
visual contrast sensitivity, as measured by low-contrast letter testing,
was more than twice as likely for those patients in the Phase 2 trial
receiving the investigational drug alemtuzumab compared to patients
receiving the active comparator Rebif.
“Low-contrast letter acuity exams are a sensitive way of measuring
visual function in MS clinical trials, and can correlate well with
structural markers of the disease,” said abstract author Laura Balcer,
MD, Associate Professor of Neurology, University of Pennsylvania School
of Medicine. “The improvements seen with alemtuzumab treatment as
compared with interferon beta are encouraging.”
During the trial, patients were asked to identify letters on
low-contrast letter charts, which capture the minimum size at which
individuals can perceive letters of a particular contrast level (shade
of gray on white background). Low-contrast sensitivity was measured for
each eye at baseline and quarterly thereafter by masked raters.
The analysis found that alemtuzumab patients were more than twice as
likely to experience sustained improvement in vision as compared to
Rebif patients (p=0.012). Alemtuzumab patients also realized a 46
percent reduction in the risk of sustained worsening in vision as
compared to Rebif treated patients (p=0.0028).
These data expand upon disability improvements as measured by the
Expanded Disability Status Scale. The EDSS is a 10-point scale in which
every 0.5-point step marks a notable deterioration in neurological
capabilities. In the Phase 2 trial, as previously reported at month 36
and 60 the mean EDSS disability score of patients receiving alemtuzumab
improved, while the mean disability worsened in the comparator group.
Alemtuzumab is a humanized monoclonal antibody being studied as a
potential therapy for relapsing-remitting multiple sclerosis.
Alemtuzumab targets the cell-surface glycoprotein CD52, which is often
expressed on T- and B-lymphocytes. Preliminary research suggests that
alemtuzumab depletes the T- and B-cells that may be responsible for the
cellular damage in MS, while potentially sparing other cells of the
immune system. Early alemtuzumab research has also suggested a
distinctive pattern of lymphocyte reconstitution in patients following
About CAMMS223 Phase 2 Study
In the Phase 2 trial, 334 patients with early active relapsing-remitting
multiple sclerosis were randomized to treatment with alemtuzumab at one
of two dose levels, or to the approved MS therapy Rebif® (high dose
interferon beta-1a). Alemtuzumab was given to patients in two or three
annual cycles of not more than five days per cycle, while Rebif was
given to patients three times per week, every week for three years. The
majority of alemtuzumab treated patients last received the
investigational drug at Month 12.
The trial successfully met its two primary endpoints, reduction in
relapse rate and reduction in the rate of sustained accumulation of
Patients were strongly encouraged to continue for two additional years
of follow-up beyond the original three years of the study. Sixty-eight
percent of alemtuzumab patients participated in the follow-up program,
and 60 percent were evaluated at 60 months. Forty-two percent of Rebif
patients participated in the follow-up program, and 35 percent were
evaluated at 60 months. Rater-blinded disability scores were assessed
quarterly and relapses as-needed. A sensitivity analysis adjusted for
patients receiving alternative disease-modifying therapy during the
follow-up period, as well as for retreatment with alemtuzumab.
As previously reported, common adverse events associated with
alemtuzumab in the CAMMS223 Phase 2 trial included mild to moderate
infusion-associated reactions, secondary autoimmunity (primarily thyroid
disorders and immune thrombocytopenia), and infections, particularly of
the upper respiratory tract; infections were predominantly mild to
moderate in severity and there were no life-threatening or fatal
infections. Approximately 30 percent of alemtuzumab-treated patients
developed an autoimmune thyroid-related adverse event. Thyroid disorders
were managed using conventional therapies. Patient monitoring for
thyroid disorders, ITP, and anti-GBM disease is incorporated into all
Genzyme-sponsored trials of alemtuzumab for the investigational
treatment of MS.
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.
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 across several areas of medicine that have
provided new hope for patients. Today, approximately 10,000 Genzyme
employees serve patients in nearly 100 countries.
Genzyme's products are focused on rare inherited disorders, kidney
disease, orthopaedics, cancer, transplant, and immune disease. The
company's commitment to innovation continues today with a substantial
development program focused on these fields, as well as cardiovascular
disease, neurodegenerative diseases, and other areas of unmet medical
need. Genzyme is part of the sanofi-aventis Group.
Sanofi-aventis, a leading global pharmaceutical company, discovers,
develops and distributes therapeutic solutions to improve the lives of
everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New
York (NYSE: SNY).
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Genzyme® is a registered trademark and CARE-MS is a service mark of
Genzyme Corporation. All rights reserved. Rebif® is a registered
trademark of EMD Serono, Inc. or affiliates.