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Medical Areas: Musculoskeletal | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Sanofi Aventis
Approval Status: Approved September 2012
Treatment Area: multiple sclerosis
Aubagio (teriflunomide) is an immunomodulatory agent with anti-inflammatory properties. The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.
Aubagio is specifically indicated for the treatment of relapsing forms of multiple sclerosis.
Aubagio is supplied as a tablet for oral administration. The recommended dose is 7 mg or 14 mg orally once daily, taken with or without food.
The FDA approval of Aubagio was based on two studies.
This double-blind, placebo-controlled study enrolled 1,088 subjects with relapsing forms of multiple sclerosis (RMS). The subjects received once daily doses of teriflunomide 7 mg and 14 mg or placebo over 108 weeks. The primary endpoint was the annualized relapse rate (ARR). The ARR was significantly reduced in both Aubagio dose groups compared to placebo: Aubagio 14mg: 0.369 (p = 0.0005); Aubagio 7mg: 0.370 (p = 0.0002); placebo: 0.539; the Relative risk reduction was 31% for both Aubagio arms. The percentage of subjects remaining relapse-free at week 108 was 56.5% in the 14mg arm, 53.7% in the 7mg arm and 45.6% in the placebo arm. The percent disability progression at week 108 was 20.2% and 21.7% in the Aubagio 14mg and 7mg arms, respectively, versus 27.3% in the placebo arm. The time to disability progression sustained for 12 weeks was statistically significantly reduced only in the Aubagio 14 mg group compared to placebo. In addition, the change in total lesion volume from baseline was significantly lower in both the Aubagio arms than in the placebo arm and both Aubagio groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than the placebo group.
This randomized, double-blind, placebo-controlled study enrolled 179 MS subjects with relapse. The subjects were treated with twice the usual dose of Aubagio for the first week and then received 7 mg or 14 mg of Aubagio or placebo for the remainder of the 36-week treatment period. The primary endpoint was the average number of unique active lesions/MRI scan during treatment. MRI was performed at baseline, 6 weeks, 12 weeks, 18 weeks, 24 weeks, 30 weeks and 36 weeks. Baseline demographics were consistent across treatment groups. The mean number of unique active lesions per brain MRI scan during the 36-week treatment period was lower in subjects treated with Aubagio 14 mg (0.98) and 7 mg (1.06) as compared to placebo (2.69), the difference being statistically significant for both (p=0.0052 and p=0.0234, respectively).
Adverse effects associated with the use of Aubagio may include, but are not limited to, the following:
- ALT increased
Mechanism of Action
Aubagio (teriflunomide) is an immunomodulatory agent with anti-inflammatory properties. It inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis.The exact mechanism by which teriflunomide exerts its therapeutic effect in multiple sclerosis is unknown but may involve a reduction in the number of activated lymphocytes in CNS.
Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center Teriflunomide added to interferon-ß in relapsing multiple sclerosis: a randomized phase II trial. Neurology 2012 Jun 5;78(23):1877-85
O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group Randomized trial of oral teriflunomide for relapsing multiple sclerosis. The New England Journal of Medicine 2011 Oct 6;365(14):1293-303
O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R; Teriflunomide Multiple Sclerosis Trial Group; University of British Columbia MS/MRI Research Group A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology 2006 Mar 28;66(6):894-900
For additional information regarding Aubagio or relapsing multiple sclerosis, please visit the Aubagio web page.