Sanofi-aventis reported today new one-year data from a Phase II study with teriflunomide, a novel oral disease modifier being investigated for the treatment of relapsing multiple sclerosis (RMS). Study results demonstrated an improvement in outcomes, with a consistent safety profile with the data from a previous Phase II monotherapy study, in patients treated with interferon beta (IFN-[BETA]) - a standard therapy in RMS - and receiving teriflunomide 7mg or 14mg, compared with patients treated with IFN-[BETA] and receiving oral placebo.

The findings were the subject of the leading oral presentation at the American Committee for Treatment and Research in Multiple Sclerosis meeting (ACTRIMS) in San Antonio, TX, USA. This study is part of a comprehensive clinical development program for teriflunomide both in monotherapy and in adjunct therapy in MS patients.

Although this Phase II study (n=116) was not powered to test for efficacy, patients taking 7mg or 14mg teriflunomide in adjunct to stable dose IFN-[BETA] experienced a significant relative risk reduction (86%; p=0.0005 and 82.8%; p<0.0001 respectively) in the number of gadolinium enhancing T1 (T1-Gd) lesions on brain magnetic resonance imaging compared with patients taking stable dose IFN-[BETA] with placebo. No unexpected safety findings have been showed with teriflunomide during the one-year period of the study as compared to the initial six-month period. Discontinuations due to treatment-emergent adverse events (TEAEs) were low and numerically similar in the three groups (placebo: 2; 7mg: 3; 14mg: 3).

"These full-year exploratory study results are encouraging as they demonstrate significant improvement in disease activity based on MRI and an acceptable safety profile associated with teriflunomide when added on top of stable therapy with IFN-[BETA]," said Mark S. Freedman, HBSc, MSc, M.D., Professor of Neurology, Department of Medicine, University of Ottawa, Ontario, Canada. "Adjunct therapy could fill an unmet medical need for those patients who are on interferon therapy but have some disease activity as measured by MRI or relapse rate. We hope to replicate the results in a Phase III study program."

A dose-dependent trend toward a relative risk reduction in the volume of brain lesions was observed with teriflunomide 7mg or 14 mg groups when used as adjunct therapy compared with placebo (72.1%; p=0.11 and 70.6%; p=0.01 respectively). There was also a dose-dependent trend to a reduction in annualized relapse rate of 32.6% (p=0.43) and 57.9% (p=0.11) in 7mg or 14mg teriflunomide adjunct groups respectively compared to IFN-[BETA] with placebo.

The most frequently reported treatment emergent adverse events were upper respiratory tract infections as a whole (placebo: 17.1%; 7mg: 16.2%; 14mg: 23.7%), mainly nasopharyngitis and sinusitis, all types of headaches (placebo: 7.3%; 7mg: 5.4%; 14mg: 18.4%), all gastrointestinal disorders (placebo: 24.4%; 7mg: 18.9%; 14mg: 31.6%). White blood cell counts decreases were numerically comparable in both teriflunomide and placebo treatment groups (placebo: 3; 7mg: 3; 14mg: 4) and no patients discontinued treatment due to neutropenia or infection. Hepatic TEAEs were mainly asymptomatic liver enzyme elevation; mostly alanine aminotransferase (ALT) increased, not exceeding three times the upper limit of the norm and no cases of concurrent increase of ALT and total bilirubine were reported.

About teriflunomide

Teriflunomide is a new oral disease modifier that blocks de novo pyrimidine synthesis thus reducing T- and B-cells proliferation with no cytotoxicity. A comprehensive clinical development program for teriflunomide has been launched in monotherapy (Phase III studies are ongoing) and in adjunct therapy (Phase II studies are closed). This Phase II study with once daily oral teriflunomide on top of IFN-[BETA] was a multicenter, placebo-controlled, double-blinded, randomized study, conducted in relapsing multiple sclerosis patients. The primary objective of the study was to evaluate the tolerability and safety of teriflunomide 7mg and 14mg in adjunct therapy with IFN-[BETA]. The one-year results of this study presented this year during the ACTRIMS congress complement the 24-weeks study results presented last year at the European Committee for Treatment and Research in Multiple Sclerosis congress (ECTRIMS). Results from a second Phase II study with teriflunomide in adjunct therapy with glatiramer acetate (GA) compared with matching placebo added to GA, were also presented this year during the American Academy of Neurology (AAN) meeting.