Teriflunomide
Teriflunomide is a experimental new drug treatment for people with relapsing remitting multiple sclerosis (MS) that is taken by mouth.
Other names: HMR1726, A771726
In development for: Relapsing remitting MS
Status: Phase III
Last updated: July 2011
How does it work?
Teriflunomide stops certain immune cells from dividing. This mode of action probably reduces the numbers of both B cells and T cells – two types of white blood cells involved in the damage associated with MS. In addition, it appears to have other immunomodulatory and anti-inflammatory actions.
Teriflunomide is closely related to leflunomide which is used to treat rheumatoid arthritis, an autoimmune condition.
How is it given?
Teriflunomide is given orally as tablets.
Clinical studies
In a phase II study involving 179 people over a period of 36 weeks, two different doses of teriflunomide were compared to placebo in people with relapsing remitting MS or with secondary progressive MS with relapses. Both doses were associated with reduced numbers of active MRI lesions and the higher dose was associated with a significantly smaller increase in disability compared to placebo.
TEMSO - Study of teriflunomide in reducing the frequency of relapses and accumulation of disability in patients with multiple sclerosis
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Pilot study of teriflunomide as adjunctive therapy to glatiramer acetate in subjects with multiple sclerosis
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Pilot study of teriflunomide as adjunctive therapy to interferon-beta in subjects with multiple sclerosis
This phase III, two year study, compared two doses of teriflunomide with placebo in 1088 people with relapsing remitting MS. Both doses of teriflunomide reduced relapse rate by about 31% compared to placebo. The higher dose (14 mg daily) reduced the risk of disability progression (sustained for 12 weeks) by 30%.
These results were reported at the 2011 annual meeting of the Academy of American Neurologists (AAN) [S41.002].
An analysis of MRI data from the TEMSO study was presented at the 21st European Neurological Meeting in Lisbon, May 2011. MRI measures of active MS lesions showed that the lower dose resulted in a 39% reduction and the higher dose a 67% reduction compared to placebo.
A phase II study in 123 people already taking glatiramer acetate (Copaxone). Participants took one of two doses of teriflunomide or placebo for 24 weeks. The main aim of this study was to assess the safety of the additional treatment with teriflunomide; results showed that the drug was well tolerated. MRI studies found that adding teriflunomide did not significantly reduce the size and volume of lesions on the brain when compared to placebo.
These results were reported at the 2010 annual meeting of the Academy of American Neurologists (AAN) [S21.001].
Similar to the study described above, 120 people already taking one of the beta interferons took one of two doses of teriflunomide or placebo for 1 year. The main aim of this phase II study was to assess how well the additional treatment with teriflunomide would be tolerated. Results indicated that addition of teriflunomide significantly improved disease control (evaluated by MRI activity) compared to beta interferon alone, with a trend to a reduction in clinical relapse, and good safety and tolerability.
These results were reported at the 2010 ACTRIMS meeting see page 27, abstract 4 of the meeting abstracts .
Further clinical trials
A number of phase II and phase III studies are currently underway or recruiting. Phase III studies are evaluating the effectiveness of teriflunomide in relapsing remitting MS compared to placebo or interferon beta-1a and in delaying conversion from a first clinical symptom suggestive of MS to clinically definite MS. A phase III study is further investigating the effectiveness of teriflunomide when added to existing beta interferon treatment.
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TEMSO extension study - Long term safety and efficacy study of teriflunomide 7 mg or 14 mg in patients with relapsing-remitting multiple sclerosis
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TOWER - An efficacy study of teriflunomide in patients with relapsing multiple sclerosis
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TENERE - a study comparing the effectiveness and safety of teriflunomide and interferon beta-1a in patients with relapsing multiple sclerosis
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TOPIC - Phase III study with teriflunomide versus placebo in patients with first clinical symptom of multiple sclerosis
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TERACLES - Efficacy and safety of teriflunomide in patients with relapsing multiple sclerosis and treated with interferon-beta
Those people completing the TEMSO study were given the opportunity to continue treatment in this extension study.
Estimated completion date September 2013.
Further details of this study.
A second phase III study comparing two doses of teriflunomide and placebo for 48 weeks in 1110 people with relapsing remitting MS. The main measure of this study will be the number of relapses per year.
Estimated completion date February 2013.
Further details of this study.
This phase III study is comparing two doses of teriflunomide with interferon beta 1a in 300 people over a treatment period of 48 weeks. The main measure of the study is the time take to treatment failure, which could be the first occurrence of a relapse or withdrawal from the study.
Estimated completion date July 2012.
Further details of this study.
This study is evaluating teriflunomide in people with a first clinical episode suggestive of MS. The main measure of the study will be the time taken to develop clinically definite MS. The study is comparing two doses and placebo in 780 people with CIS (clinically isolated syndrome).
Estimated completion date December 2018. Currently recruiting participants.
Further details of this study. More details of the study, including UK study centres are available from the TOPIC study website.
This phase III study aims to recruit 1455 participants worldwide. The study will compare relapse rates while taking one of two doses of teriflunomide or placebo added on to existing beta interferon treatment over a treatment period of between 48 to 152 weeks.
Estimated completion date April 2014. Currently recruiting participants.
Further details of this study.
Side effects and contraindications
Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups. Headaches and nausea were both reported.
References
O'Connor PW et al.
A phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses.
Neurology 2006;66(6):894-900.
Read abstract