Genzyme, a Sanofi company, has announced that the FDA ( Food and Drug Administration ) has approved Aubagio ( Teriflunomide ) as a new once-daily, oral treatment indicated for patients with relapsing forms of multiple sclerosis. Aubagio has shown significant efficacy across key measures of multiple sclerosis disease activity, including reducing relapses, slowing the progression of physical disability, and reducing the number of brain lesions as detected by MRI.
The FDA approval was based on efficacy data from the TEMSO ( TEriflunomide Multiple Sclerosis Oral ) trial. In the Phase III TEMSO trial, Teriflunomide 14 mg significantly reduced the annualized relapse rate ( p=0.0005 ) and the time to disability progression ( p=0.0279 ) at two years versus placebo in patients with relapsing forms of multiple sclerosis.
Teriflunomide 7 mg significantly reduced the annualized relapse rate ( p=0.0002 ) in the trial.
The Aubagio label includes a boxed warning citing the risk of hepatotoxicity and teratogenicity ( based on animal data ).
In MS clinical studies with Teriflunomide, the incidence of serious adverse events were similar among Teriflunomide and placebo-treated patients. The most common adverse events associated with Teriflunomide in multiple sclerosis patients included increased ALT levels, alopecia, diarrhea, influenza, nausea and paresthesia.
The labeling for Aubagio was also informed by the estimated 2.1 million years of patient exposure globally since the launch of Leflunomide, which is indicated in the United States for the treatment of rheumatoid arthritis. Teriflunomide is the principal active metabolite of Leflunomide. Severe liver injury including fatal liver failure has been reported in patients treated with Leflunomide.
The Aubagio clinical development program in multiple sclerosis also included the TOWER study. TOWER assessed the efficacy and safety of once-daily, oral Teriflunomide in patients with relapsing forms of multiple sclerosis. In the study, patients receiving Teriflunomide 14 mg had a statistically significant reduction in annualized relapse rate and risk of disability progression. In addition, a significant reduction in annualized relapse rate was observed in patients treated with Teriflunomide 7 mg compared to placebo. Adverse events observed in the trial were consistent with previous clinical trials with Teriflunomide in multiple sclerosis.
Teriflunomide is an immunomodulator with anti-inflammatory properties. Although the exact mechanism of action for Teriflunomide is not fully understood, it may involve a reduction in the number of activated lymphocytes in the central nervous system ( CNS ). ( Xagena )
Source: Genzyme, 2012