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Paris, France – September 11, 2009
Encouraging phase II results with teriflunomide in patients with relapsing multiple sclerosis
Safety and efficacy data presented at the 2009 ECTRIMS.
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced
today the results of a phase II study with teriflunomide a novel orally available immunomodulatory therapy
for multiple sclerosis (MS). In a 24-week study, teriflunomide when added to background stable therapy with
interferon (IFN-beta) showed acceptable tolerance and safety (primary endpoints) and showed significant
improvements of the disease as measured by magnetic resonance imaging (MRI) with the two doses tested
versus placebo. These results were presented today at the 25th Congress of the European Committee for
Treatment and Research in Multiple Sclerosis (ECTRIMS).Teriflunomide is currently being explored in a
phase III program for relapsing forms of MS.
With regard to efficacy, disease control as assessed through MRI activity measures, improved beyond that
achieved with IFN-beta therapy alone as shown by reductions in cerebral inflammatory lesions compared to
placebo (56% with 7mg, 81% at 14mg, both p<0.001). Only few clinical relapses were reported in each
group over the 24-week treatment period.
“This exploratory study shows that teriflunomide can be administered on top of stable therapy with interferon
with an acceptable safety and tolerability profile” said Mark S. Freedman, HBSc, MSc, MD - Professor of
Neurology, Department of Medicine, University of Ottawa, Ontario, Canada. “Although the study was not
powered to test for efficacy, we were pleased to see a significant additional effect of teriflunomide over
interferon-beta alone in reducing MRI activity measures. These results encourage longer term studies to
establish the clinical benefit of combination treatment in this disease where effective new therapies are
eagerly awaited.”
Approximately 90% of patients completed the 24-week treatment period in each group. Treatment was
prematurely discontinued for treatment-emergent adverse events (TEAEs) in one patient in each group. The
proportion of patients with TEAEs due to increased alanine aminotransferases (ALT) was higher on 14mg
(28.9%) than on 7mg (13.5%) or placebo (12.2%). Among them, the proportion of patients with ALT greater
than 3xULN (upper limit of normal) was low (4.8% in placebo; 0% in 7mg; 5.2% in 14mg) with one
treatment discontinuation from placebo and one from 14mg. No cases had associated bilirubin increase.
The proportion of patients with TEAEs potentially related to immunosuppression (including white blood cell
counts, infections and infestations) was higher in the teriflunomide groups (placebo: 32%, 7mg: 49%, 14
mg: 47%). Among these events upper respiratory tract infections (nasopharyngitis, sinusitis) appeared to be
more frequent at 14mg (23.7%) than placebo (14.6%) and 7mg (10.8%). None of these events led to
treatment discontinuation. Overall the safety profile was similar to what has been previously reported for
teriflunomide. *
Teriflunomide is a selective inhibitor of de novo pyrimidine synthesis which modulates the proliferation of Tand
B-lymphocytes, and has antiproliferative and anti-inflammatory properties. In this 24-week double blind,
placebo-controlled, randomized, 3-arm multinational phase II clinical study conducted in 116 patients with
relapsing-remitting MS, patients received, one of the two study doses (7mg or 14mg once daily) or placebo
on top of stable background therapy with IFN- beta. The study primary endpoints were the tolerability and
safety of 7mg and 14mg doses of teriflunomide administered orally once daily. Efficacy was assessed
based on MRI activity measures and patients’ relapses were recorded over the course of the study.
* O’ Connor, Neurology, 2006
About teriflunomide
Teriflunomide is a novel orally available immunomodulatory therapy in multiple sclerosis (MS), currently
under investigation. It is a selective inhibitor of de novo pyrimidine synthesis which exerts a cytostatic effect
on proliferating T- and B-lymphocytes in the periphery, and thus has antiproliferative and anti-inflammatory
properties.
A proof-of-concept clinical trial in patients with relapsing forms of MS has demonstrated that teriflunomide
monotherapy significantly reduces MRI activity and improves clinical endpoints, effects that are maintained
with long term treatment. Phase III for monotherapy is currently ongoing.
In addition, the effects of early intervention with teriflunomide in patients with a clinically isolated syndrome
consistent with demyelination are also being evaluated thus making the extensive development programme
of teriflunomide (~3,000 patients) one of the widest of any of the new oral disease-modifying agents; it is
hoped it will bring a new treatment both effective and with identified and manageable risks to the market.
About Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, progressive, degenerative neurological disease, mediated by immune
system dysregulation, culminating in demyelination and axonal damage within the central nervous system.
MS imposes a significant burden on patients, and is one of the most common neurological diseases in
young adults, and the leading cause of non-traumatic disability in young and middle-aged adults. An
estimated two million people are living with MS worldwide, and with global population growth, its prevalence
is expected to increase. Although significant progress in MS treatment has been made over the last two
decades, most notably with the emergence of disease-modifying therapies - all administered parenterally,
not all patients have full disease control and the use of additional therapy in conjunction with IFN-β or
glatiramer acetate might offer further benefit to patients.
About MRI
The magnetic resonance imaging (MRI) is a complementary examination currently used for the diagnosis of
multiple sclerosis in association to clinical examination. It also allows to measure the activity of the disease
(activity of the lesions) and contributes to the assessment of the treatments in the clinical studies.
About ECTRIMS
The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS ) is a representative
European organization that facilitates communication and creates synergies among clinicians and scientists
to promote and enhance research and improve clinical outcomes in multiple sclerosis.
About sanofi-aventis
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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