Teriflunomide

Parent company: Sanofi

• Oral medication taken daily.
  
  
• This drug is an immunomodulator that affects the production of T and B cells. It inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. It may inhibit nerve degeneration by reducing the production of free radicals, possibly decreasing the risk of infections and other complications linked to chemotherapy-like drugs.
  
  
• The TEMSO trial for RRMS compared 7 and 14 mg of teriflunomide in 1,088 individuals. Both doses significantly reduced the annualized relapse rate by approximately 31 percent. Teriflunomide (7-mg dose) resulted in a 39.4- percent reduction in brain lesion volume on MRI compared with placebo; the 14-mg dose resulted in a 67.4-percent reduction. The 14-mg dose also reduced the risk of sustained disability progression by 29.8 percent relative to placebo. The number of gadolinium-enhancing lesions were also reduced with both doses compared with placebo, and there was a trend toward a greater effect with the higher dose.
  
  
• A Phase III extension study of TEMSO is now underway. Patients who completed the original study and who received the drug are being maintained on the same dose; those who received placebo are randomized to teriflunomide 7 mg or 14 mg. The study remains double-blinded.
  
  
• The TOWER efficacy study of 1,110 individuals with RRMS is scheduled from August 2008 to February 2013. It will test 7-mg and 14-mg doses versus placebo. Its primary endpoint is the annualized relapse rate; the secondary endpoint is time to disability progression. Results of this second of two placebo-controlled Phase III trials, which are required to support an application for regulatory approval, are expected in 2012.
  
  
• The ongoing Phase III TOPIC study of 780 individuals with clinically isolated syndrome (CIS) is scheduled from February 2008 to November 2015; it is still recruiting participants. It also is comparing 7- and 14-mg teriflunomide versus placebo. The study's primary endpoint is the time to conversion to clinically-definite MS after CIS. Several secondary endpoints include: MRI findings; relapse rate; disability and progression. The drug's safety will also be evaluated.
  
  
• The TENERE Phase III study is comparing 7- and 14-mg teriflunomide with Rebif in 300 people. It is scheduled from April 2009 to July 2012.
  
  
• Following a Phase II study indicating that combined treatment with teriflunomide appears to be superior to an interferon given alone, the TERACLES Phase III study began in January 2011 and is scheduled for completion in April 2014; it is currently recruiting 1,455 participants. The study will compare relapse rateswhile taking a 7- or 14-mg dose of teriflunomide or placebo, in combination with an existing interferon treatment. The primary outcome measure is the annualized relapse rate. Secondary outcome measures include: MRI findings; disability progression; time to a first confirmed relapse; and the proportion of patients who are relapse-free.