The pivotal phase III TEMSO study with investigational once-daily oral medication Teriflunomide ( Aubagio ) has been published in The New England Journal of Medicine ( NEJM ). The results have shown that Teriflunomide at the 14mg dosage significantly reduced the annual relapse rate, reduced disability progressions and improved several magnetic resonance imaging ( MRI ) measures of disease activity, including new or worsening brain lesions.

The two-year TEMSO ( TEriflunomide Multiple Sclerosis Oral ) trial involved 1,088 people with relapsing forms of multiple sclerosis from 126 Centers across 21 countries.
TEMSO findings showed that, compared to placebo, Teriflunomide once daily:

significantly reduces the risk of annual relapses, the primary endpoint, by 31% ( both p<0.001 ) for 7mg and 14mg doses;

significantly increases the time to first relapse, and allows significantly more trial participants to remain free of relapses during the two years of the study: 53.7% ( 7mg, p=0.01 vs. placebo ), 56.5% ( 14mg, p=0.003 vs. placebo ) and 45.6% ( placebo );

the risk of 12-week confirmed disability progression, the key secondary endpoint, was significantly reduced by 30% ( p=0.03 ) for the 14mg dose and numerically reduced by 24% ( p=0.08 ) for the 7mg dose;

improved several standard magnetic resonance imaging ( MRI ) measures of disease activity as compared to placebo including new or worsening brain lesions with an apparent dose dependent effect in favor of the 14mg dose:

a) reduced burden of disease ( by 39.4% [ p=0.03 ] and 67.4 % [ p<0.001 ] for 7mg and 14mg, respectively );

b) reduced Gadolinium-enhancing T1 lesions ( relative risk reduction of 57% and 80%, p<0.001 for both doses );

c) reduced unique active lesions per scan ( relative risk reduction of 48% and 69%, p<0.001 for both doses ).

Similar adverse events, serious adverse events, and adverse events leading to treatment discontinuation were observed with Teriflunomide compared to placebo. No serious or opportunistic infections and no deaths occurred in trial participants treated with Teriflunomide. The proportion of participants who discontinued the study medication because of disease progression was significantly smaller in the group receiving the 14mg of Teriflunomide than in the placebo group ( p=0.02 ). Malignancies were reported in three participants in the placebo group and one in the Teriflunomide 14mg group.
Teriflunomide adverse events were usually of mild to moderate intensity, managed with existing therapies and rarely led to treatment discontinuation. The most common were diarrhea, nausea, liver enzyme increases ( that were mainly mild and asymptomatic with no dose effect ) and mild hair thinning/decreased hair density. In general, diarrhea, nausea and alopecia, were mild to moderate, transient, and infrequently led to treatment discontinuation.

Teriflunomide is an immunomodulatory, disease-modifying oral drug with anti-inflammatory properties, and is under investigation for the treatment of multiple sclerosis. Teriflunomide blocks the proliferation and functioning of activated T and B lymphocytes, which are thought to be especially damaging in multiple sclerosis, by selectively and reversibly inhibiting a critical mitochondrial enzyme. Slowly dividing or resting lymphocytes are unaffected by Teriflunomide, leaving the immune system’s response to infection uncompromised.

Source: Sanofi, 2011

XagenaMedicine2011


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