AUBAGIO Rx

Four randomized, controlled, double-blind clinical trials established the efficacy of Aubagio in patients with relapsing forms of multiple sclerosis.

Study 1 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 26 months in patients with relapsing forms of multiple sclerosis. Patients were required to have a diagnosis of multiple sclerosis exhibiting a relapsing clinical course, with or without progression, and to have experienced at least 1 relapse over the year preceding the trial or at least 2 relapses over the 2 years preceding the trial. The primary endpoint was the annualized relapse rate (ARR).

Patients (n=1088) were randomized to receive Aubagio 7 mg (n=366), Aubagio 14 mg (n=359), or placebo (n=363). At trial entry, patients had an Expanded Disability Status Scale (EDSS) score ≤5.5; mean age of 38 years, mean disease duration of 5 years, and mean EDSS at baseline of 2.7. 

Findings showed a statistically significant reduction in ARR for patients who received Aubagio 7 mg (0.370, P=0.0002) or 14 mg (0.369, P=0.0005), compared to those who received placebo (0.539). There was a consistent reduction of the ARR noted in subgroups defined by sex, age group, prior multiple sclerosis therapy, and baseline disease activity.

There was a statistically significant reduction in the relative risk of disability progression at week 108 sustained for 12 weeks (as measured by at least a 1-point increase from baseline EDSS ≤5.5 or a 0.5 point increase for those with a baseline EDSS >5.5) in the Aubagio 14 mg (20.2%, P <0.05) group compared to placebo (27.3%).

The effect of Aubagio on several magnetic resonance imaging (MRI) variables, including the total lesion volume of T2 and hypointense T1 lesions, was assessed in Study 1. The change in total lesion volume from baseline was significantly lower in the Aubagio 7 mg (0.755, P=0.0317) and 14 mg (0.345, P=0.0003) groups than in the placebo group (1.127). Patients in both Aubagio groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than those in the placebo group (0.570, P <0.0001 and 0.261, P <0.0001 vs 1.331, respectively).

Study 2 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 40 months in patients with relapsing forms of multiple sclerosis. Patients were required to have a diagnosis of multiple sclerosis exhibiting a relapsing clinical course and to have experienced at least 1 relapse over the year preceding the trial, or at least 2 relapses over the 2 years preceding the trial. The primary end point was the ARR.

Patients (n=1165) received Aubagio 7 mg (n=407), Aubagio 14 mg (n=370), or placebo (n=388). At trial entry, patients had a mean age of 38 years, a mean disease duration of 5 years, and a mean EDSS at baseline of 2.7. 

At study end point, there was a statistically significant reduction in the ARR for patients who received Aubagio 7 mg (0.389, P=0.0183) or 14 mg (0.319, P=0.0001) compared to those who received placebo (0.501). There was a consistent reduction of the ARR noted in subgroups defined by sex, age group, prior multiple sclerosis therapy, and baseline disease activity.

There was a statistically significant reduction in the relative risk of disability progression at week 108 sustained for 12 weeks (as measured by at least a 1-point increase from baseline EDSS ≤5.5 or a 0.5 point increase for those with a baseline EDSS >5.5) in the Aubagio 14 mg (15.8%, P <0.05) group compared to placebo (19.7%).

Study 3 was a double-blind, placebo-controlled clinical trial that evaluated once daily doses of Aubagio 7 mg and 14 mg for up to 108 weeks in patients with relapsing multiple sclerosis. Patients were required to have had a first clinical event consistent with acute demyelination occurring within 90 days of randomization with 2 or more T2 lesions at least 3 mm in diameter that were characteristic of multiple sclerosis. 

Patients (n=614) received Aubagio 7 mg (n=203), Aubagio 14 mg (n=214), or placebo (n=197). At trial entry, patients had a mean age of 32 years, EDSS at baseline of 1.7, and mean disease duration of two months. Results showed that the proportion of patients free of relapse was greater in the Aubagio 7 mg (70.5%, P <0.05) and 14 mg (72.2%, P <0.05) groups than in the placebo group (61.7%).

Study 4 was a randomized, double-blind, placebo-controlled clinical trial that assessed the effect of Aubagio in multiple sclerosis patients with relapse based on MRI activity. 

The MRI scan was to be performed at baseline, 6 weeks, 12 weeks, 18 weeks, 24 weeks, 30 weeks, and 36 weeks after treatment initiation. A total of 179 patients were randomized to Aubagio 7 mg (n=61), Aubagio 14 mg (n=57), or placebo (n=61). Baseline demographics were consistent across treatment groups. The primary endpoint was the average number of unique active lesions/MRI scan during treatment.

The mean number of unique active lesions per brain MRI scan during the 36-week treatment period was lower in patients treated with Aubagio 7 mg (1.06) and 14 mg (0.98) as compared to placebo (2.69), the difference being statistically significant for both (P=0.0234 and P=0.0052, respectively).