In the U.S., the once-daily therapy was approved in September 2012 for adults with relapsing forms of MS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS.
Aubagio became available in the European Union in August 2013 for adults with RRMS and, in June 2021, its use was expanded to include patients as young as 10 years old, becoming the first oral therapy available as first-line treatment for pediatric MS patients.
However, a similar label expansion was rejected by the U.S. Food and Drug Administration (FDA), which stated that available data at that time were not sufficient to grant Aubagio’s approval for younger patients.
Since November 2018, the FDA has approved generic forms of Aubagio from four companies: Glenmark Pharmaceuticals, Sandoz (now a subsidiary of Novartis), Accord Healthcare, and Alembic Pharmaceuticals.
While generics have the same active ingredients and are required to work in the same way as brand-name medicines, they are less expensive due to lower development costs. However, these will likely only become commercially available after 2026, when Sanofi’s patents for Aubagio for relapsing forms of MS expire.
How Aubagio works
Aubagio is an active metabolite of leflunomide, a medication used to treat rheumatoid arthritis. It works by blocking the activity of dihydroorotate dehydrogenase, an enzyme essential for the proliferation of activated immune T- and B-cells, without affecting survival of non-activated and slowly-dividing cells.
Both T- and B-cells are involved in inflammatory reactions believed to promote the loss of the protective myelin sheath around nerve fibers, a hallmark of MS, subsequently leading to neurodegeneration. Aubagio was also reported to reduce the levels of pro-inflammatory molecules produced by T-cells.
Aubagio in clinical trials
Aubagio’s ability to reduce the rate of MS relapses and prevent the risk of disease progression in people with relapsing forms of MS was demonstrated in a number of Phase 2 and 3 trials.
The global Phase 3 TEMSO 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 either 7 mg of Aubagio, 14 mg of Aubagio, or a placebo, once daily, for about two years.
Results showed that treatment with Aubagio significantly reduced the mean annual relapse rate by 31% and the higher dose significantly lowered the risk of disability progression, measured with the expanded disability status scale, by 29.8% compared with a placebo.
Both doses were superior to placebo at reducing several MRI-based measures of disease activity, including the number and extension of brain lesions. The therapy was generally well-tolerated, with similar rates of adverse events and serious adverse events between Aubagio and placebo groups.
A post-hoc analysis, or one conducted after the trial is over, also demonstrated that, compared with placebo, Aubagio significantly reduced relapses leading to hospitalization, the number of nights spent in the hospital due to relapses, annual rates of all hospitalizations, and emergency room visits.
A total of 742 patients completing TEMSO chose to enter its extension study (NCT00803049), in which all maintained their assigned doses or were switched randomly to either dose of Aubagio for about six years.
Up to nine years of combined data from TEMSO and its extension study showed that the therapy remained generally safe with longer-term treatment and led to reductions in mean annual relapse rates and brain lesions in patients switching to Aubagio, rates which remained low thereafter. Patients’ disability remained mild and stable in the extension study.
In a second, global, Phase 3 trial, called TOWER (NCT00751881), 1,169 adults with relapsing MS were randomly assigned to receive either one of the two doses of Aubagio or a placebo, once daily, for at least one year.
TOWER’s results confirmed TEMSO’s findings, with both doses of Aubagio significantly lowering patients’ mean annual relapse rates by 22.3%–36.3%, and the high dose significantly reducing the risk of three-month confirmed disability progression by 31.5%, relative to a 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.
The Phase 3 TENERE trial (NCT00883337) compared the safety and effectiveness of Aubagio (7 mg and 14 mg) against Rebif (interferon beta-1a) in 324 adults with relapsing MS. Rebif, given through under-the-skin injections, is an established treatment for relapsing forms of MS.
Results showed that treatment with the higher dose of Aubagio had similar effects to Rebif in terms of mean annual relapse rates, but Aubagio was associated with higher patient-reported treatment satisfaction.
Also, in a Phase 3 trial called TOPIC (NCT00622700), both doses of Aubagio were found to significantly reduce the risk of conversion to clinically definite MS in adults with CIS — by 37.2%–42.6%, relative to a placebo. Aubagio treatment was also associated with lower disease-associated brain shrinkage in these patients.
Moreover, patients across the U.S. and 13 other countries reported high levels of satisfaction with the efficacy and convenience of Aubagio in a post-marketing clinical study called Teri-PRO (NCT01895335).
The ongoing, international Phase 3 TERIKIDS clinical trial (NCT02201108) is evaluating the safety and effectiveness of two years of treatment with Aubagio against a placebo in 166 children, ages 10 to 17, with relapsing forms of MS. Aubagio is being given at doses equivalent to those approved for adults.
After completing TERIKIDS, which was set to finish in September 2021, patients had the option of enrolling in an open-label extension study, and receive treatment with Aubagio for up to two years.
Results indicated the therapy reduced the risk of relapse by 34% relative to placebo, but this difference did not reach statistical significance, failing to meet the trial’s main goal.
Still, compared with placebo, Aubagio was associated with a significant, 43% reduction in the risk of clinical relapse or high MRI activity and with significantly fewer new or enlarging brain lesions. The therapy was generally well-tolerated in this pediatric population.
Aubagio’s common side effects include headache, diarrhea, nausea, hair loss, skin irritation, and occasional breathing problems.
According to Sanofi, patients with liver or kidney problems should consult with a physician before taking Aubagio. In addition, women who are planning to conceive or are pregnant should avoid the therapy, so as to avoid potential harm to the unborn child.
Last updated: Sept. 13, 2021
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