FDA-Approved Medications: Administered Orally
Companies: Genzyme, a Sanofi company
- Oral medication (tablet form) taken daily; two doses approved: 7 mg and 14 mg
- Approved for relapsing forms of MS
Aubagio (teriflunomide) contains the same active ingredient as leflunomide, which has been used in the treatment of rheumatoid arthritis since 1998. This drug is an immuno-modulator that affects the production of T and B cells. It inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Unlike some drugs that modulate the immune system, Aubagio is thought to leave the immune system’s response to infection intact, so it may still fight against infection while a patient is taking this drug. It may also inhibit nerve degeneration by reducing the production of free radicals. (Free radicals can damage cells in the brain and other organs.)
Aubagio was the second oral medication to be FDA-approved for relapsing forms of MS, and became available in October 2012. Both a 7-mg and 14-mg daily dose were approved, although the 14-mg dose proved to be more effective in clinical trials.
People taking Aubagio are advised to be checked for exposure to tuberculosis (TB) prior to starting this medication, as several cases of TB occurred in trials. Liver function tests must be performed monthly for the first six months while on Aubagio, and periodically thereafter. Hair loss is another potential side effect, although this can be transient.
Aubagio is considered Pregnancy Category “X,” and both men and women of child-bearing potential should use effective birth control while taking Aubagio. As the drug can remain in the body for up to two years, this is an important consideration to plan in advance. If pregnancy is contemplated, a rapid decrease of Aubagio levels in the blood can be induced by taking cholestyramine or activated charcoal. The process takes 11 days.
Prior to approval, Aubagio successfully completed several large clinical trials. The TEMSO trial for RRMS compared 7 mg and 14 mg of Aubagio in 1,088 individuals. Both doses significantly reduced the annualized relapse rate by approximately 31 percent. The 14-mg dose also reduced the risk of sustained disability progression by 29.8 percent relative to placebo. Aubagio (7-mg dose) resulted in a 39.4-percent reduction in brain-lesion volume on MRI compared with placebo; the 14-mg dose resulted in a 67.4-percent reduction. The number of gadolinium-enhancing lesions were also reduced with both doses compared with placebo, and a trend toward a greater effect was observed with the higher dose. No difference in the rate of serious infection, opportunistic infection, or malignancy was found.
A Phase III extension study TEMSO is ongoing. Patients who completed the original study and who received the drug are being maintained on the same dose; those who received placebo are randomized to Aubagio 7 mg or 14 mg. The study remains double-blinded, and will evaluate safety and efficacy. Preliminary data presented in 201330 found no new or unexpected adverse events (AE) associated with long-term (up to nine years) exposure to Aubagio. Adverse events were consistent with the two-year core trial, and incidence of adverse events generally decreased and remained low.
Results of the TOWER study of 1,169 individuals with RRMS were reported in the fall of 2012.31 The results showed a 36.3-percent reduction in ARR with Aubagio (14 mg), versus placebo. There was also a significant 37-percent risk reduction in the number of patients who were relapse-free during the trial and a 31.5-percent reduction in the risk for 12-week sustained accumulation of disability versus placebo. Results for the 7-mg dose showed a significant but smaller reduction in relapse rate but not in sustained accumulation of disability.
A third Phase III study called TENERE32 compared the two oral doses of Aubagio to Rebif. The primary endpoint was time to the first occurrence of confirmed relapse or permanent treatment discontinuation for any reason, whichever came first. In the study, 48.6 percent of patients receiving the 7-mg dose of Aubagio and 37.8 percent of those on the 14-mg dose relapsed or discontinued treatment, compared to 42.3 percent of patients on Rebif. However, the rate of permanent treatment discontinuation was lower with Aubagio (18.3 and 19.8 percent) than Rebif (28.8 percent).
The Phase III TOPIC study33 of 618 individuals with clinically isolated syndrome (CIS) reported data in 2013. This study also compared 7-mg and 14-mg doses of Aubagio versus placebo. The study’s primary endpoint was the time to conversion to clinically-definite MS (CDMS) after CIS. The study was ended early as revised diagnostic criteria have enabled earlier diagnosis of MS.
The 14-mg dose of Aubagio reduced the risk of second MS relapse (and thus reduced the risk of conversion from CIS to “clinically definite MS”) by 43 percent. Safety and efficacy were consistent with the other Phase III Aubagio studies. This highlighted the ability of early treatment with this disease-modifying therapy to delay the onset of MS attacks.