|This section's factual accuracy may be compromised due to out-of-date information. (September 2012)|
|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Biological half-life||2 weeks|
|Molecular mass||270.207 g/mol|
|(what is this?)|
Teriflunomide (trade name Aubagio, marketed by Sanofi) is the active metabolite of leflunomide. Teriflunomide was investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis (MS). The study was completed in July 2010. 2-year results were positive. However, the subsequent TENERE head-to-head comparison trial reported that "although permanent discontinuations [of therapy] were substantially less common among MS patients who received teriflunomide compared with interferon beta-1a, relapses were more common with teriflunomide." The drug was approved by the FDA on September 13, 2012 and in the European Union on August 26, 2013.
Mechanisms of action
Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase. It is uncertain whether this explains its effect on MS lesions.
Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Teriflunomide may decrease the risk of infections compared to chemotherapy-like drugs because of its more-limited effects on the immune system.
Activation of leflunomide to teriflunomide
Teriflunomide is the main active in vivo metabolite of leflunomide. Upon administration of leflunomide, 70% of the drug administered converts into teriflunomide. The only difference between the molecules is the opening of the isoxazole ring. This is considered a simple structural modification and a technically simple one-step synthetic transformation. Upon oral administration of leflunomide in vivo, the isoxazole ring of leflunomide is opened and teriflunomide is formed.
“Regardless of the substance administered (leflunomide or teriflunomide), it is the same molecule (teriflunomide)—the one exerting the pharmacological, immunological or metabolic action in view of restoring, correcting or modifying physiological functions, and does not present, in clinical use, a new chemical entity to patients.” Because of this, EMA had not considered teriflunomide being a new active substance.
See Leflunomide for information on pharmacokinetics, side-effects, contraindications and other data.
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- ClinicalTrials.gov Phase III Study of Teriflunomide in Reducing the Frequency of Relapses and Accumulation of Disability in Patients With Multiple Sclerosis (TEMSO)
- "Sanofi-Aventis’ Teriflunomide Comes Up Trumps in Two-Year Phase III MS Trial". 15 Oct 2010.
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- EU authorisation details, EMA, retrieved 2014-04-29
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- European Medicines Agency. Committee for Medicinal Products for Human Use. (27 June 2013). "Summary of Opinion (Initial Authorisation of Aubagio /teriflunomide/)" (PDF). European Medicines Agency (http://www.ema.europa.eu/ema/). Retrieved 5 June 2015.
- AUBAGIO® (teriflunomide) 14 mg tablets — Aubagio website