Last updated on April 17, 2014 at 10:21 EDT

Oral Therapy Teriflunomide (Aubagio(TM)(*)) Significantly Reduces Relapses Leading to Hospitalization of Patients with Multiple Sclerosis

October 20, 2011

PARIS, October 20, 2011 /PRNewswire/ –

– New findings from the pivotal TEMSO Phase III study presented today at
the joint ECTRIMS / ACTRIMS Congress -

– U.S. FDA Accepts New Drug Application for Teriflunomide for relapsing
forms of MS -

Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme
announced today new data from the pivotal TEriflunomide Multiple Sclerosis
Oral (TEMSO) Phase III trial showing that once-daily oral teriflunomide
significantly reduced annualized rates of relapses leading to
hospitalization. New data also confirmed the safety profile and efficacy of
teriflunomide over a six-year period after the initial randomization. A
total of fifteen presentations on teriflunomide are on the program for the
fifth joint triennial congress of the European and American Committee for
Treatment and Research in Multiple Sclerosis (ECTRIMS / ACTRIMS) in
Amsterdam, Netherlands.

The companies also announced today that the U.S. Food and Drug
Administration has accepted for review Sanofi’s new drug application (NDA)
for oral teriflunomide as a potential therapy for people with relapsing
forms of multiple sclerosis (MS). Sanofi expects to file an application for
regulatory approval with the European Medicines Agency (EMA) in the first
quarter of 2012.

“The new results of the TEMSO study show that both 7mg and 14mg doses of
teriflunomide could reduce the severity of relapses measured through annual
rates of relapses leading to hospitalization as well as deliver encouraging
long-term results on safety and efficacy,” said Professor Paul O’Connor,
Director of the MS Clinic at St. Michael’s Hospital, Toronto, Canada, and
principal investigator of the TEMSO study.

New post-hoc analyses showed that teriflunomide-treated patients’
annualized rate of relapses leading to hospitalization was significantly
reduced by 36% (p=0.015) with 7 mg and by 59% (p<0.0001) with 14 mg compared
with placebo. The risk of hospitalization per relapse was also significantly
reduced by 43% (p<0.001) for the 14 mg dose and numerically reduced by 6%
(p=NS) for the 7 mg dose. These analyses also showed teriflunomide
significantly reduced the annualized rate of emergency medical facility
visits (a visit to a medical facility/hospital for emergency care not
resulting in an admission) by 42% (p=0.004) for the 14 mg dose and
numerically reduced by 31% (p=NS) for the 7 mg dose vs placebo.

“The additional data presented at ECTRIMS further supports the potential
of teriflunomide as a new once a day oral therapy that can significantly
decrease the number of relapses requiring hospitalizations for patients
suffering from this complex and unpredictable disease and who need safer and
more effective therapeutic options,” said Dr. Elias Zerhouni, President,
Global Research & Development, Sanofi.

Long-term data on safety and efficacy of teriflunomide were also
presented at this congress. The results from the extension of the TEMSO
study showed that both doses of teriflunomide were well tolerated six years
after the initial randomization, with a consistent safety profile to the
core two- year study. The beneficial effects of teriflunomide on clinical
and MRI endpoints reported in TEMSO also continue to be sustained over five
years after the initial randomization.

In addition to the TEMSO extension, the follow up to the Phase II
long-term efficacy and safety study was presented. These new findings showed
that teriflunomide was well tolerated up to nine years of continuous
exposure, with a safety profile consistent with that reported during the 36
weeks of initial double-blind treatment. The reductions in disease activity
observed with teriflunomide in the initial study were maintained for up to
eight years of treatment.

About TEMSO study

TEMSO was a two-year randomized, double-blind, placebo-controlled
multinational study that included 1,088 people with relapsing forms of MS
from 126 centers in 21 countries. Trial participants were 18-55 years of
age, with an Expanded Disability Status Scale (EDSS) of 5.5 or less, and had
at least one relapse in the previous year or at least two relapses in the
preceding two years. Trial participants were randomized to placebo or
teriflunomide, 7mg or 14mg, once daily and followed for 108 weeks. The
primary endpoint was annualized relapse rate, defined as the number of
confirmed relapses per trial participant year; a relapse is a new or
worsening of a previous clinical sign or symptom. The key secondary endpoint
was the time to sustained disability progression, measured by the EDSS.
Disability progression was defined as an increase from baseline of at least
1.0 point on the EDSS persisting for at least 12 weeks. Change from baseline
in total lesion volume was also a key prespecified MRI endpoint in the
study. Safety and tolerability evaluations were based on adverse events,
physical examinations, vital signs and laboratory investigations. A
long-term extension of TEMSO is ongoing.

About Teriflunomide

Teriflunomide is an immunomodulatory, disease-modifying oral drug with
anti-inflammatory properties, and is under investigation for the treatment
of relapsing forms of MS. Teriflunomide blocks the proliferation and
functioning of activated T and B lymphocytes – which are thought to be
especially damaging in MS – by selectively and reversibly inhibiting a
critical mitochondrial enzyme. With nine years of continuous use in a Phase
II extension, teriflunomide has the longest clinical experience of any
investigational oral MS therapy. In addition to the TEMSO trial, two other
Phase III trials, TOWER and TENERE, are ongoing in people with RMS. A Phase
III study, TOPIC, is also underway in early MS or CIS (clinically isolated
syndrome). Teriflunomide is also being evaluated as an adjunct therapy to
interferon-beta in the Phase III TERACLES trial.

(*) Aubagio(TM) is the proprietary name submitted to health authorities
for the investigational agent teriflunomide.

About Multiple Sclerosis

Today more than 2,000,000 people around the world suffer from MS, a
chronic autoimmune disease that affects the central nervous system – the
brain, spinal cord and optic nerves. In MS, immune cells called lymphocytes
mistakenly attack myelin, the fatty “insulation” that surrounds and protects
nerves, resulting in abnormal nerve transmission and MS symptoms such as
fatigue, weakness, walking and balance problems, vision problems, pain,
spasticity and cognitive difficulties. MS is the most common disabling
neurological disease in young adults after accidents, and is two to three
times more common in women than in men. MS is usually characterized by
relapses followed by periods of complete or incomplete recovery. There is no
typical individual with MS, as the disease is a very variable condition and
the symptoms depend on which areas of the central nervous system are
affected. MS symptoms can vary from time to time and can change in severity
and duration, even in the same person.The vast majority of people with MS -
approximately 90 percent – are initially diagnosed with a relapsing form of

Magnetic resonance imaging (MRI) is a common and important tool used to
help establish a diagnosis of MS and monitor the course of the disease and
effects of treatment. Providing a highly sensitive, non-invasive way to
image the brain, spinal cord or, other areas of the body, MRI has made it
possible to visualize and understand a great deal about the underlying
pathology of MS.

About Genzyme, a Sanofi Company

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. The
company’s areas of focus are rare genetic diseases, multiple sclerosis,
cardiovascular disease, and endocrinology. Genzyme is a Sanofi company.
Genzyme’s press releases and other company information are available at
http://www.genzyme.com .

Genzyme’s Multiple Sclerosis business unit is responsible for the
development of teriflunomide, along with the investigational MS therapy

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).

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
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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 labeling and other matters that could
affect the availability or commercial potential of such products candidates,
the absence of guarantee that the products 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 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 update or revise any forward-looking information
or statements.


Source: PR Newswire