Sanofi-aventis announced the initiation of a multinational phase III study evaluating the efficacy and safety of two doses of once daily teriflunomide (7mg or 14mg) versus placebo in patients with relapsing multiple sclerosis (RMS) treated with interferon beta (IFN ß). Teriflunomide is a novel oral disease modifier developed by sanofi-aventis which is being investigated in a large phase III clinical development programme. It includes studies of teriflunomide in monotherapy for the treatment of RMS and in clinically isolated syndrome as well as adjunct therapy.

“Initiation of the TERACLES study is a tremendous milestone as it is the first ever phase III study of an oral drug in adjunct therapy to be launched in multiple sclerosis,” said Marc Cluzel, M.D., Ph.D., executive vice president, research & development, sanofi-aventis. “We are confident that teriflunomide is an excellent candidate for assessing innovative adjunct therapy in multiple sclerosis considering the positive effect observed when it was used in adjunct with interferon beta in the phase II study.”

Specifically, the TERACLES study will evaluate whether once daily oral teriflunomide 14 or 7mg, in patients treated for at least 6 months on a stable dose of IFN ß prior to randomization, can reduce the annualized relapse rate (primary endpoint) compared to IFN ß plus oral placebo tablets. The main secondary endpoints of the study are to document the disease activity measured by MRI, the time to disability progression and overall safety.

“The purpose of the TERACLES study is to assess the clinical benefits of teriflunomide as an adjunct therapy in patients with relapsing multiple sclerosis,” said Mark S. Freedman, HBSc, MSc, M.D., Professor of Neurology, Department of Medicine, and University of Ottawa, Ontario, Canada. “We hope that this study will replicate the additional efficacy and safety profile we observed in the Phase II trial with teriflunomide in adjunct with interferon beta, and bring an innovative therapeutic approach to this patient population.”

The phase II study results presented this year during the ACTRIMS congress showed that teriflunomide in adjunct with IFN ß significantly improved disease control (evaluated by MRI activity) beyond IFN ß plus oral placebo at one year, with a trend towards fewer clinical relapses and with a consistent safety profile with the data from a phase II monotherapy study.

Approximately 240 study sites in 28 countries are targeted for participation in the TERACLES study which will involve 1455 RMS patients. The first patient is expected to be enrolled before the end of this year and the trial will end once the last patient recruited has received at least 48 weeks of treatment.

Teriflunomide is a new chemical entity being studied in a far-reaching and ambitious clinical program including more than 3.500 patients in 36 countries. Teriflunomide has previously been evaluated as an adjunct therapy to either interferon ß or glatiramer acetate in two phase II studies. Results of these studies were presented earlier this year during the American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and American Academy of Neurology (AAN) meetings respectively. In one of this Phase II study, teriflunomide in adjunct to glatiramer acetate (GA) was well-tolerated compared to patients receiving GA and placebo. Although there was a numerical trend for the reduction in number and volume of gadolinium enhancing T-1 brain MRI lesions in the adjunct arm compared to placebo with GA, the relative effect was not as robust as that observed for teriflunomide with IFN ß. Teriflunomide is also being investigated in a monotherapy clinical development program. TEMSO phase III trial positive results have been presented during the last European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress and showed that teriflunomide successfully reduces annualized relapses rate (primary study endpoint) vs placebo and was well tolerated in MS patients. Two other phase III trials, TOWER and TENERE, are also ongoing in RMS patients. A phase III study, TOPIC, completes the clinical development in early MS or CIS (Clinically isolated syndrome).