Aubagio (teriflunomide) is an approved oral treatment for relapsing forms of multiple sclerosis (MS) that helps to reduce the risk of relapses and delay disability progression, while also lessening measures of brain damage on MRI scans.
The brand-name medication is marketed by Sanofi. However, more than a dozen generic forms of Aubagio have been approved by the U.S. Food and Drug Administration (FDA) since 2018.
Generics have the same active ingredients and are required to work in the same way as brand-name medicines, but are usually less expensive. While Sanofi’s patents for Aubagio do not expire until 2026, the first generics are expected to become commercially available in 2023, under an agreement with Sanofi.
Aubagio is an active metabolite of leflunomide, a medication approved for treating rheumatoid arthritis. It works by blocking the activity of dihydroorotate dehydrogenase, an enzyme essential for the growth of activated immune cells, namely T-cells and B-cells.
These immune cells are involved in the inflammatory attacks that damage the protective myelin sheath around nerve fibers, a hallmark of MS. By blocking this enzyme, Aubagio stops the activated cells from replicating, without affecting the survival of nonactivated and slowly dividing cells. The reduction in activated immune cells is thought to lessen MS-driving inflammation.
The FDA approved Aubagio in 2012 for treating adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS.
Aubagio is approved in more than 80 countries, according to Sanofi. However, in some regions, such as Canada and the European Union, the medication is solely approved for people with RRMS.
In the European Union, Aubagio was approved for adults with RRMS in 2013, but its use was expanded in 2021 to include children and adolescents ages 10 and older. This made Aubagio the first oral first-line treatment available for pediatric MS patients in Europe.
A similar label expansion was rejected by the FDA, which stated that available data were not sufficient to grant an approval for younger patients.
Aubagio is not recommended for certain groups of patients, including:
Aubagio is available in film-coated tablets that come in two strengths:
The recommended dose is 7 mg or 14 mg, taken by mouth once per day, with or without food.
A number of Phase 2 and 3 trials demonstrated Aubagio’s ability to reduce the rate of MS relapses and prevent the risk of disease progression in people with relapsing forms of MS.
The global TEMSO Phase 3 trial (NCT00134563) evaluated the safety and effectiveness of Aubagio in 1,088 adults with relapsing MS, who were randomly assigned to receive an oral tablet of Aubagio (7 mg or 14 mg) or a placebo, once daily for about two years.
Results showed that treatment with Aubagio significantly reduced the mean annual relapse rate by 31% compared with a place. The higher dose also significantly lowered the risk of disability progression by 29.8% relative to the placebo. Both doses reduced several MRI-based measures of disease activity, including the number and extension of brain lesions.
A total of 742 patients completing TEMSO chose to enter its extension study (NCT00803049), in which all received one of the two doses of Aubagio for about six years.
Up to nine years of combined data from TEMSO and its extension study showed the therapy remained generally safe and led to reductions in mean annual relapse rates and brain lesions in patients switching to Aubagio — rates that remained low thereafter. Patients’ disability levels remained mild and stable in the extension study. The therapy also was associated with slower disease-associated brain shrinkage, or atrophy, and improved cognitive function.
In a second global Phase 3 trial, called TOWER (NCT00751881), 1,169 adults with relapsing MS — with two relapses in the prior two years or one relapse in the previous year — were randomly assigned to receive either Aubagio (7 mg or 14 mg) or a placebo, taken once daily for at least one year.
TOWER’s results confirmed TEMSO’s findings, with both doses of Aubagio significantly lowering the mean annual relapse rates by 22.3%–36.3% relative to a placebo. Additionally, the high dose significantly reduced the risk of three-month confirmed disability progression by 31.5%, compared to the placebo.
A total of 751 patients completing TOWER’s core study chose to join its open-label extension phase, in which all were given the high dose of Aubagio (14 mg) for up to six years. Data from the extension study confirmed a favorable long-term safety and efficacy profile of the high dose of Aubagio. Both disability worsening and relapse rates remained low and stable over the course of the extension study.
TENERE (NCT00883337), also a Phase 3 trial, compared the safety and effectiveness of Aubagio (7 mg and 14 mg) against the widely approved medication Rebif (interferon beta-1a) in 324 adults with relapsing MS. Rebif, given through under-the-skin (subcutaneous) injections, is an established treatment for relapsing forms of MS.
The higher dose of Aubagio induced similar reductions in annual relapse rates as Rebif, trial results showed, but Aubagio was associated with higher patient-reported treatment satisfaction.
In a post-marketing clinical study called Teri-PRO (NCT01895335), patients across the U.S. and 13 other countries also reported high levels of satisfaction with the efficacy and convenience of Aubagio.
In a Phase 3 trial called TOPIC (NCT00622700), both doses of Aubagio significantly reduced the risk of conversion to clinically definite MS in adults with CIS — by about 40%, compared with a placebo. Aubagio treatment also was associated with smaller changes in brain volume in these patients.
The international Phase 3 TERIKIDS clinical trial (NCT02201108) evaluated the safety and effectiveness of Aubagio against a placebo in 166 children, ages 10 to 17, with relapsing forms of MS.
Aubagio was given for two years at doses equivalent to those approved for adults. Participants who completed TERIKIDS, or who showed evidence of high disease activity during the trial, could then enroll in an open-label extension study and receive Aubagio for up to two years.
Results from TERIKIDS showed that the median time to a first disease relapse was longer for patients given Aubagio than for a placebo (75.3 weeks vs. 39.1 weeks). However, the reduction in relapse risk was not statistically significant, failing to meet the trial’s main goal.
Notably, more participants in the placebo group than the Aubagio group had switched to the open-label portion of the study due to high disease activity — which may have affected the study’s ability to detect significant differences.
A pre-specified analysis showed that the risk of disease relapse or high activity leading to the switch to the open-label portion was significantly reduced, by 43%, in patients treated with Aubagio. Aubagio treatment also outperformed the placebo across several MRI measures of disease activity. In addition, rates of adverse events (side effects) were generally similar among patients given Aubagio or a placebo.
The most common side effects associated with Aubagio include:
Aubagio carries a boxed warning for severe liver injury, which can occur at any time during treatment and can be life-threatening. Liver function should be checked before starting on Aubagio, and regularly monitored while taking the medication. If liver injury is suspected, treatment should be stopped.
Because Aubagio is excreted from the body very slowly, patients who need to stop treatment for safety reasons are recommended to undergo an accelerated elimination procedure to quicken the removal of the therapy from the body. This involves 11 days of treatment with activated charcoal or cholestyramine, a medication commonly used to lower cholesterol levels.
The prescribing information for Aubagio also carries a boxed warning that it can cause damage to a developing fetus. As such, the medication should not be given to anyone who is or is planning to become pregnant. Patients who are able to become pregnant should use effective contraception while on Aubagio.
Those who become pregnant while on Aubagio may enroll in an observational study (NCT03198351), sponsored by Sanofi, that is monitoring the outcomes of pregnancies exposed to Aubagio.
Some patients can develop an allergic reaction to Aubagio. The treatment should be stopped if such a reaction occurs, and patients should seek immediate medical care.
Skin reactions, which may be life-threatening, can also be experienced by patients taking Aubagio. Those experiencing symptoms such as rash, redness and peeling of the skin, and mouth sores or blisters should discontinue Aubagio and seek immediate medical care.
Treatment with Aubagio can reduce immune cell counts, which also can increase the risk of infections. Immune cell levels should be assessed before starting the therapy, and patients should be monitored for signs of infection.
Those with active infections should not take Aubagio, and the treatment may need to be suspended in cases in which a serious infection develops.
Some patients receiving Aubagio can show signs of peripheral neuropathy, meaning damage to nerves outside of the brain and spinal cord. This can result in numbness or tingling sensations in the hands or feet that are different from usual MS symptoms. This problem is more common in patients older than 60, in those who have diabetes, and in people taking certain medications that affect the nervous system.
Aubagio may increase blood pressure, which should be monitored before and periodically during treatment. Those with elevated blood pressure should be appropriately managed during Aubagio treatment.
Patients on Aubagio can experience disorders associated with scarring of lung tissue. Those who develop symptoms such as cough and shortness of breath should be examined for lung health and may need to discontinue treatment.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Aubagio was approved by the U.S. Food and Drug Administration in September 2012 for adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Since 2018, more than a dozen generic formulations of Aubagio have also been cleared in the U.S., but those will only become commercially available starting in 2023.
Based on animal data, Aubagio may cause harm to a developing fetus. Human data suggest that taking Aubagio in the first trimester of pregnancy followed by an accelerated elimination procedure is not associated with an increased rate of malformations or miscarriage. However, the number of pregnancies reported in these studies is not sufficient to draw conclusions. Thus, Aubagio is not recommended for anyone who is pregnant or planning a pregnancy. Patients able to become pregnant should use effective contraception while receiving this therapy.
There are no known interactions between Aubagio and alcohol. But because both can cause liver damage, people who drink alcohol while on Aubagio may have a greater likelihood of experiencing such side effects. Patients receiving the medication should discuss with their healthcare providers whether and how much alcohol is safe for them to drink.
Because not all patients respond to a treatment in the same way, there is no standard timeline for when Aubagio might become effective. Patients should talk with their healthcare provider about when and how Aubagio is expected to help in their particular case.
Hair thinning or hair loss (alopecia) has been reported as one of the most common side effects of Aubagio, affecting up to 13% of patients in clinical trials. This side effect is mostly mild to moderate and becomes evident about three months after starting therapy. It does resolve spontaneously in most patients without stopping treatment. Weight gain has not been reported in studies as a side effect associated with Aubagio.
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