#AANAM – Aubagio at Higher Dose Shows Long-term Efficacy in Variety of Patients, Trial Data Show

Aubagio taken as 14 milligram (mg) tablet once daily significantly reduces the risk of relapse in people with relapsing multiple sclerosis (MS) over time irrespective of their prior treatment history, a pooled analysis of Phase 2 and Phase 3 trial results show.

The findings were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, in the poster “Long-Term Effect of Teriflunomide in Subgroups Defined by Prior Treatment: Pooled Analysis of the Phase 2 Study and Phase 3 TEMSO, TOWER, and TENERE Core and Extension Studies.”

Aubagio (teriflunomide), marketed by Sanofi Genzyme, is an oral anti-inflammatory therapy for relapsing MS, approved by the U.S. Food and Drug Administration and the European Commission. It is often used as a first treatment or first switch-therapy.

Its efficacy and safety have been established in several clinical trials, including a Phase 2 study — NCT01487096, and its extension trial NCT00228163 — and the Phase 3 TEMSO (NCT00134563), TOWER (NCT00751881), and TENERE (NCT00883337) clinical trials, and their extensions.  

Overall, clinical data showed that Aubagio at both 7 mg and 14 mg once a day could effectively reduce the incidence of MS relapse events, and prevent the risk of disease progression.

These studies enrolled relapsing MS patients, categorized into subgroups depending on whether they had a prior treatment (and type of treatment): those who were treatment-naïve (no treatment for two years before joining the trial); those recently treated with Aubagio at 7 mg (core studies started some patients at 7 mg before moving them to 14 mg in extension trials); and those recently treated with another disease-modifying therapy (DMT), further subdivided into patients who discontinued that DMT within 6 months prior to enrolling in an Aubagio study, and those who stopped using a different DMT between six months and two years before.

Other DMTs included in the analysis were Novartis’ Gilenya (fingolimod), Teva’s Copaxone (glatiramer acetate), interferon beta therapies, Biogen’s Tysabri (natalizumab), and Aubagio at 7 mg.

In this pooled post-hoc analysis of all Aubagio trials, researchers evaluated the long-term efficacy and safety of its use in patients categorized by type of prior MS treatment (including those who were using no treatment in the two years prior to an Aubagio study’s start and were classified as treatment naive).

They compared the adjusted annualized relapse rates (ARRs) and the risk of disability worsening in each subgroup to patients who had been randomized to a control (placebo) group or to 14 mg of Aubagio.

The pooled analysis included 1,695 patients treated with Aubagio at 14 mg daily, of whom 1,021 had been treatment naïve, 353 had taken Aubagio at 7 mg, 158 had used another DMT within six months of a study’s start (called a baseline measure), and 163 patients who had stopped another DMT in the longer time group.

The analysis showed that treatment with Aubagio 14 mg significantly reduced the risk of relapse compared with placebo, irrespective of the type of prior treatment. Their adjusted ARRs with that 14 mg daily dose dropped by 35%, 45%, and 34%  respective to the groups detailed above.

The risk of disability worsening at four years was similarly lower, and Expanded Disability Status Scale (EDSS) scores remained stable across all subgroups from baseline up to year eight.

Treatment-related side effects that led to stopping Aubagio’s use were lower in the group recently treated with the 7 mg dose (both 7 mg and 14 mg were approved by the FDA), and similar between all other subgroups. They included a rise in liver enzymes, headache, diarrhea, hair thinning and nausea, and all were considered mild to moderate and transient. No new or unexpected safety issues were reported.

These findings show that Aubagio at 14 mg effectively lowers disability in the long-term in relapsing MS patients, irrespective of their prior treatment preferences, the researchers concluded.

“People living with MS often switch treatments several times throughout the course of their disease, and making decisions around treatment sequencing can be challenging,” Patricia K. Coyle, MD, director of the MS Comprehensive Care Center at Stony Brook, New York, said in a press release.

“This analysis being presented at AAN is helpful, as it shows that relapsing MS patients treated with Aubagio experienced a significantly reduced risk of relapse, regardless of previous treatment status,” Coyle added.