In a clinical trial involving 1,169 people with relapsing-remitting multiple sclerosis, oral teriflunomide (Genzyme/Sanofi-Aventis) reduced relapses compared with placebo over at least 48 weeks, according to a company press release dated June 1, 2012. Of two different doses tested during the TOWER trial, the higher dose also slowed progression of disability. This is the third completed of five phase III studies involving teriflunomide in multiple sclerosis. An application for marketing approval of teriflunomide was accepted for review by the U.S. Food and Drug Administration in October 2011.
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. In the TEMSO study reported in 2011, teriflunomide reduced the average number of MS relapses and disease activity on MRI scans significantly more than inactive placebo in 796 people with relapsing forms of MS. Read more about this study.
In the TENERE study, compared with Rebif® (interferon beta-1a, EMD Serono and Pfizer), teriflunomide did not significantly reduce the primary endpoint of “risk of failure,” meaning the first occurrence of a relapse, or permanent discontinuation of the study treatment, whichever came first. Read more about this study.
Other phase III studies of teriflunomide are ongoing, including the TOPIC study in 780 people at high risk for developing MS (teriflunomide vs. placebo); and the TERACLES study in 1455 people with relapsing MS (teriflunomide vs. placebo added on to interferon beta).
The Study: For the TOWER trial, investigators worldwide recruited 1,169 people with relapsing MS, and randomly assigned them to receive teriflunomide 7 mg or 14 mg, once daily by mouth, or placebo for 48 weeks. The primary endpoint was whether the study drug reduced the average number of relapse per year significantly more than placebo. Secondary endpoints included the time to disability progression confirmed for at least 12 weeks.
According to the press release, Teriflunomide 14 mg reduced relapses by 36.3% versus placebo and 7 mg reduced relapses by 22.3% versus placebo. In the 14 mg-group, the time to disability progression was reduced by 31.5%; the lower dose did not significantly reduce progression.
Three deaths occurred in the teriflunomide groups – from sepsis, suicide, and motor vehicle accident. Participants in the teriflunomide groups experienced more headache, nausea, diarrhea, hair thinning, and low levels of white blood cells.
Comment: These and results from additional phase III studies of teriflunomide that have been completed or are now underway should help define the short-term safety and promise of teriflunomide as a potential new therapy for relapsing MS.
Rebif is a registered trademark of EMD Serono and Pfizer.