24-Month Study Confirms Efficacy of Oral Fingolimod in MS

New Orleans, LA — Results from the FREEDOMS II trial found oral fingolimod administered at a daily dose of 0.5 mg to reduce relapse rates by almost 50% in patients with relapsing-remitting multiple sclerosis (RRMS). The drug also had positive effects on all magnetic resonance imaging (MRI) parameters, including brain atrophy. These findings confirm the benefits of fingolimod reported in previous phase 3 studies of this first oral treatment for RRMS.

The FREEDOMS II trial randomized 1083 patients with RRMS to fingolimod 0.5 mg, 1.25 mg, or placebo, in a 1:1:1 ratio. Participants were treated for 24 months. The trial included enrollment of 95% of patients from the United States. The mean duration of multiple sclerosis (MS) was slightly more than 10 years. Three-fourths of the participants had undergone prior treatment with other disease-modifying therapy. About 72% of patients enrolled in the trial completed this study.

Fingolimod administered at a daily dose of 0.5 mg significantly reduced the annualized relapse rate by 48% compared with placebo (P <.001), and increased the percentage of patients free of MS relapse at the end of 24 months compared with placebo (71.% versus 52.7%, respectively).

Brain atrophy was significantly reduced with daily treatment of 0.5 mg of fingolimod versus placebo at month 24: 33% reduction in brain volume versus placebo (P <.001). The effect on brain volume was seen as early as 6 months (39% reduction) and was consistent at 12 (40% reduction) and 24 months.

Although numerically fewer patients treated with 0.5 mg of fingolimod experienced disability progression, as measured by change in Expanded Disability Status Scale (EDSS), this difference did not reach statistical significance. Lead author of this poster, Peter A. Calabresi, MD, MS Center at Johns Hopkins Hospital, Baltimore, MD, suggested that this might be due to the high variability in baseline EDSS scores among the 3 treatment arms.

Disability, as measured by the MS Functional Composite (MSFC), was significantly less at month 24 in the group treated with fingolimod daily dose of 0.5 mg versus placebo (P = .012). Fingolimod, administered at 0.5 mg, was superior to placebo on all MRI assessments of gadolinium-enhancing lesions and new or newly enlarging T2 lesions.

Fingolimod’s safety profile in this study was consistent with reported adverse events associated with this treatment. In this trial, the incidences of herpes infections, hypertension, and basal cell carcinoma were higher, but pooled analysis from 3 pivotal phase 3 trials and a phase 2 study did not confirm these findings.