Teriflunomide, being developed as a potential oral treatment for multiple 
sclerosis (MS) by sanofi-aventis, is the active metabolite of the rheumatoid 
arthritis drug leflunomide. Both teriflunomide and leflunomide are inhibitors of 
the mitochondrial enzyme dihydroorotate dehydrogenase, which is critically 
involved in pyrimidine synthesis. The production of activated T-cells largely 
depends on de novo pyrimidine synthesis, and thus pyrimidine depletion is 
thought to result in the inhibition of immune cell proliferation. Therapeutic 
efficacy of teriflunomide has been demonstrated in vivo in an experimental 
autoimmune encephalomyelitis model of MS using Dark Agouti rats. In a phase II, 
randomized, double-blind, placebo-controlled clinical trial of patients with 
relapsing-remitting MS, treatment with teriflunomide reduced the number of 
active lesions in the brain and preliminary evidence indicated a slowing in the 
development of disability. Recently reported data from the phase III TEMSO 
clinical trial support these initial findings. Compared with current therapies, 
teriflunomide has the advantage of oral administration. Thus, if good efficacy 
is demonstrated, teriflunomide may have a role to play in the future treatment 
of MS.