Aubagio® (teriflunomide)

FDA-Approved Medications: New Data on Previously Approved Medications

Company: Genzyme

  • Oral; 7 mg or 14 mg once daily
  • Approved for RMS in 2012

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As with many other disease-modifying therapies (DMTs) for MS, the exact mechanism by which Aubagio® (teriflunomide) exerts its therapeutic effect has not yet been fully determined. In the case of Aubagio, the mechanism may involve reducing the number of activated lymphocytes – immune-system cells – in the central nervous system. The medication has anti-inflammatory properties and has been shown to inhibit the synthesis of pyrimidine, an organic compound involved with various cells and processes throughout the body.43

Aubagio secured FDA approval for use in RMS following positive results from four randomized, controlled, double-blind clinical trials. In the first study, 1,088 patients were randomized in a 1:1:1 ratio to receive Aubagio 7 mg, Aubagio 14 mg, or placebo, and were followed for up to 26 months. Individuals receiving Aubagio had a statistically significant reduction in the annual relapse rate (ARR) – the study’s primary endpoint – compared to those receiving placebo. The second study followed 1,165 patients for up to 40 months, also randomizing them in a 1:1:1 ratio to receive Aubagio 7 mg, Aubagio 14 mg, or placebo, and specifying ARR as the primary endpoint. Both doses of Aubagio again showed statistically significant advantages over placebo in terms of a lower relapse rate and on other measures of efficacy.43

The third study followed a similar design in terms of randomization and endpoint but focused on people who had experienced a first clinical event consistent with acute demyelination (damage to protective nerve fibers in the brain) occurring within 90 days of randomization. After following these individuals for up to 108 weeks (two years and four weeks), the study found that significantly higher proportions of Aubagiotreated patients remained free of relapse, compared with those receiving placebo. The fourth study examined MRI characteristics of 179 individuals with RMS. The mean number of active lesions per MRI scan of the brain during the 36-week treatment period was lower in people treated with Aubagio 7 mg (1.06) and Aubagio 14 mg (0.98) than with placebo (2.69). The difference was statistically significant for both.43

New data show low ARRs in patients who previously received no DMT or who switched to Aubagio from another DMT. A post-hoc analysis of data from a Phase II study and from the Phase III TEMSO, TOWER, and TENERE studies identified 2,643 patients who received Aubagio 14 mg/d or placebo and had received another DMT or no therapy before switching to Aubagio or placebo. The participants were divided into three groups: those who discontinued another DMT six months before randomization (348), those who stopped another therapy six months to two years before randomization (412), and those who received no prior DMT (1,883). ARRs ranged from 0.33 to 0.53 for the three groups, and the mean rates were all significantly lower than those for placebo.44

Meanwhile, a separate post-hoc analysis showed that long-term Aubagio use reduced brain-volume loss. Researchers identified individuals who had received Aubagio 14 mg/d (214) or placebo (197) during the Phase III TOPIC study, which measured the efficacy of Aubagio in people with a first clinical episode suggestive of MS. The investigators used an automated brainmeasurement system to calculate brain-volume loss at six-month intervals over two years. At endpoint, an overall 43-percent reduction in whole-brain-volume loss was reported with Aubagio use, and the median percentage of brain-volume loss was significantly lower in the Aubagio-treatment group compared with the placebo group. Median reductions in whole-brain-volume loss at six, 12, and 18 months were 87 percent, 29 percent, and 36 percent, respectively, in the Aubagio-treatment group.15

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