Aubagio Shows Long-term Safety, Efficacy in Relapsing MS Extension Study

Aubagio (teriflunomide), taken as a 14 mg tablet once a day, shows long-term safety and efficacy in patients with relapsing forms of multiple sclerosis (MS), according to results of the Phase 3 TOWER extension study.

Treatment was generally well tolerated by the 751 patients using Aubagio for a median of 4.2 years, and up to 6.3 years, in this extension trial, with side effects remaining consistent with those reported in earlier studies, and long-term disease stabilization evident, its researchers reported.

These results are in the study “Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study,” published in the journal Multiple Sclerosis and Related Disorders.

Aubagio, an approved MS therapy marketed by Sanofi Genzyme, proved to be safe and effective in treating relapsing forms of MS, including relapsing-remitting MS (RRMS), in the Phase 3 TOWER trial (NCT00751881) as well as in several other trials.

For lifelong conditions such as MS, however, therapies must remain effective and tolerable for patients over long periods of time.

An international team of researchers assessed the long-term safety and efficacy outcomes from the extension study of the TOWER clinical trial.

TOWER’s core study had randomly assigned patients, all of whom had at least one relapse in the previous year, to a placebo (253 patients), or to treatment with Aubagio at 7 mg (265 people) or at 14 mg (233 patients) for at least 48 weeks. Depending on the time of their enrollment, participants received treatment for a maximum of 152 weeks (almost three years).

In total, 751 patients moved into the extension study, whose main goal was to establish the “long-term safety and tolerability” of Aubagio at the 14 mg dose.

Other study endpoints included confirmed disability worsening over a 12-week period (12-week CDW), as measured on the expanded disability status scale (EDSS). Another goal was tracking patients’ relapse rates.

Both disability worsening and relapse rates remained low and stable over the course of the extension study. Average EDSS scores remained unchanged over time among all treatment groups: those moving from placebo or Aubagio at 7 mg to its 14 mg dose, and those continuing with 14 mg daily from the core study.

Confirmed 12-week disability worsening was lower among patients assigned to Aubagio at either dose in the core study compared with those assigned to placebo: 12.3% lower for patients initially on 7 mg Aubagio and 23.9% lower for those who started on 14 mg tablets. This different was significant for the extension study’s first year, but not in subsequent years, the researchers wrote.

Disability progression was also significantly lower among the two continuous treatment groups over the first year of the extension study, with no significant differences among all three groups noted over later years.

According to the researchers, this indicated that delaying the start of Aubagio treatment did not reduce its clinical efficacy.

Patients on continuous 14 mg Aubagio showed significantly lower relapse rates than those given a placebo in the core study. After switching to Aubagio in the extension period, however, these people showed similar responses to treatment.

“The probability of confirmed MS relapse was significantly reduced in both the 7 mg/14 mg … groups compared with the placebo/14 mg group [placebo initially; 14 mg for extension] in the core study; however, no significant differences were apparent across groups in the extension,” the researchers wrote.

Most patients who left after the core study, declining to enter the extension did so because of side effects, across all three groups — placebo and the two Aubagio arms, the study noted. Lack of efficacy was the second most common reason given.

Few serious adverse events throughout the extension period were reported, although the rate of such events was lower among initial placebo group patients (6.4%) than those given either dose of Aubagio (12.4%) in the core study.

The most frequently reported side effects were nasopharyngitis (common cold; 102 patients), headache (68 patients) and diarrhea (65 patients).  The most common serious adverse events included infections (13 patients), increases in alanine aminotransferase levels (a sign of liver damage; 4 patients), increases in creatine phosphokinase (a sign of injury or stress to muscle tissue; 4 participants), and MS relapse (3 patients).

Adverse events of special interest included disorders of the blood and liver, peripheral neuropathy, and evidence of cancer. These occurred rarely and uniformly across all groups.

Hair thinning was more frequent among patients who initially given a placebo (14.3%) compared with those who received Aubagio (4.5% in the 7 mg group, and 4.3% in those in the 14 mg group).

Overall, the extension study showed that Aubagio 14 mg was well-tolerated for up to 6.3 years of treatment. No new or unexpected adverse events were reported and safety observations remained consistent with those of the core study. Delaying treatment initiation did not carry significant long-term consequences.

Taken together, “these findings demonstrate the long-term safety and efficacy of teriflunomide in [relapsing] MS patients regardless of when treatment is initiated, but support the earlier initiation of treatment to minimize relapses,” the researchers concluded.