Results of successful phase III trial of oral teriflunomide for relapsing MS – reduced relapses, MRI disease activity, and higher dose reduced disability progression
October 5, 2011
Oral teriflunomide (Sanofi-Aventis) reduced the average number of MS relapses in a year significantly more than inactive placebo is a study of 796 people with relapsing forms of MS. The therapy also reduced the volume of tissue damage and active areas of damage in those who were taking teriflunomide compared to placebo at the end of the two-year trial. These TEMSO study results were previously reported at medical meetings, and Paul O’Connor, MD (University of Toronto) and colleagues have now published the complete results in The New England Journal of Medicine (2011;365:1293-303). The study was sponsored by Sanofi-Aventis.
Background: Multiple sclerosis occurs when the immune system attacks the brain and spinal cord. Teriflunomide is a novel oral compound that inhibits the function of specific immune cells. Other phase 3 studies of teriflunomide are ongoing, including the TOWER study of 1110 people with relapsing forms of MS; the TOPIC study in 780 people at high risk for developing MS; and studies of teriflunomide in combination with approved disease-modifying therapies.
The Study: In the TEMSO trial, 1088 people with relapsing MS were randomly assigned to receive 7 mg teriflunomide, 14 mg teriflunomide, or inactive placebo for 108 weeks; 796 (73.2%) completed the study. The primary endpoint measured was the average number of relapses in a year, and secondary endpoints included disability progression using the EDSS disease activity scale, disease activity on MRI scans, and measures of fatigue.
Results: After two years, both doses of teriflunomide significantly reduced the average number of relapses in a year by as much as 31.5% over placebo. Fewer of those on the higher dose (14mg) experienced progression of disability compared with those on placebo (20.2% progressed on therapy vs. 27.3% on placebo); there was a trend toward less progression in those at the lower dose but it was not statistically significant. On imaging scans, the total volume of tissue damage and active areas of damage were reduced significantly more in both teriflunomide groups than in the placebo group. No significant differences were reported in brain tissue volume changes, or in fatigue.
Safety: No serious infections were observed in participants, and no deaths occurred. Three cases of serious kidney infection occurred in the 14-mg group, with one resulting in discontinuation of study medication. The most common side effects experienced by those on teriflunomide were nausea, diarrhea, mildly elevated liver enzymes and thinning of the hair. Reductions in white blood cells were slightly higher in the 14-mg teriflunomide group than the other groups, and stabilized over time. Increased blood pressure was higher in the teriflunomide groups than in the placebo group, but no patient discontinued treatment because of blood pressure issues.
Comment: These positive results are the first phase III results of oral teriflunomide for treating relapsing forms of MS. These and results from additional phase III studies of teriflunomide now underway should help define the short-term safety and promise of teriflunomide as a potential new therapy for relapsing MS. The long-term impacts, benefits, and potential adverse events of teriflunomide and other emerging therapies are still to be determined.