Teriflunomide significantly reduced the annualized relapse rate in patients with relapsing-remitting multiple sclerosis by more than one-third, compared with placebo, in the second of two large, randomized, phase III trials that have been conducted with the drug.
The latest study, called TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis), demonstrated that the 14-mg dose of teriflunomide produced a 36% relative risk reduction in the annualized relapse rate, compared with placebo (P = .0001). A 7-mg dose of the oral MS agent yielded a 22% relative risk reduction (P = .0183).
Teriflunomide 14 mg, but not 7 mg, was also associated with a significantly lower sustained disability accumulation than placebo.
"These data support the use of teriflunomide as an initial therapy for patients with relapsing-remitting multiple sclerosis and as an option for patients who are unable to tolerate other disease-modifying therapies," wrote the TOWER Trial Group investigators (Lancet Neurol. 2014 Jan. 23 [doi: 10.1016/S1474-4422(13)70308-9]).
First author Dr. Christian Confavreux of University Claude Bernard Lyon 1, France, and his associates commented that the findings add to those previously reported from the phase III TEMSO trial (N. Engl. J. Med. 2011;365:1293-303), which showed that teriflunomide 7 mg and 14 mg both reduced the annualized relapse rate by around 31% when compared with placebo. They are also supported by the results of a phase II extension study.
Teriflunomide was approved for the treatment of adults with relapsing-remitting MS in the United States (trade name Aubagio) in 2012 and in Europe in 2013. The drug is the principal active metabolite in leflunomide, which is licensed for the treatment of rheumatoid arthritis.
The TOWER trial involved a total of 1,169 patients with relapsing-remitting MS who were randomized to treatment: 408 were assigned to teriflunomide 14 mg, 372 to teriflunomide 7 mg, and 389 to placebo. The mean age of patients at study entry was approximately 38 years, with just over 80% being of white, 15% of Asian, and 2% of black ethnicity.
The annualized relapse rates were 0.50 for patients treated with placebo, 0.32 for patients treated with teriflunomide 14 mg, and 0.39 for those treated with teriflunomide 7 mg. Absolute risk reductions for teriflunomide 14 mg and 7 mg versus placebo were –0.11 and –0.18, respectively.
A key secondary endpoint was sustained accumulation of disability. This was defined as an increase of at least 1 point on the Expanded Disability Status Scale (EDSS) from baseline that persisted for at least 12 weeks. The hazard ratios for the time to sustained accumulation of disability were 0.68 (P = .0442) for the 14-mg dose of teriflunomide and 0.95 for the 7-mg dose versus placebo.
"The safety and tolerability profile of teriflunomide, as characterized in this and previous studies, was similar for both the 7-mg and 14-mg doses, including long-term treatment observations," the investigators wrote. The most common side effects seen in patients treated with teriflunomide were hair thinning, headache, and increase in alanine aminotransferase concentrations.
Genzyme, a Sanofi company, sponsored the trial. The investigators disclosed financial relationships with Genzyme as well as other companies that manufacture drugs used to treat MS.