News Briefs From the 28th Congress of ECTRIMS

Patients who completed the trial were followed for between 48 and 173 weeks. The average duration of teriflunomide exposure in TOWER was 18 months.

Adverse events observed in the trial were consistent with those seen in previous studies of teriflunomide in MS.

The proportion of patients with treatment-emergent adverse events was similar across all treatment arms. The most common adverse events reported more frequently in the treatment arms were headache, ALT (alanine aminotransferase) elevations, hair thinning, diarrhea, nausea, and neutropenia. As previously reported, there was one death from a respiratory infection in the placebo arm and three deaths in the teriflunomide arms. The three deaths in the treatment arms were attributed to a motor vehicle accident, a suicide, and sepsis.

Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis required for proliferation of rapidly dividing lymphocytes. Teriflunomide thus limits expansion of stimulated T- and B-cells thought responsible for the damaging inflammatory process associated with MS while preserving resting lymphocytes’ function for immune surveillance. Teriflunomide is marketed by Genzyme under the brand name Aubagio. The drug was approved by the FDA on September 12, 2012 as a once-daily, oral immunomodulator indicated for patients with relapsing forms of MS.

Long-Term Safety and Efficacy Data Released for Oral Fingolimod
Four-year data from the phase III FREEDOMS extension study highlight the sustained efficacy of oral fingolimod and reinforce the known safety profile.

At the 28th Congress of ECTRIMS, Ludwig Kappos, MD, and his colleagues presented postmarketing data on the efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (MS) receiving continuous or placebo-fingolimod switched therapy for as many as four years.

Dr. Kappos and colleagues reported that after switching from placebo to fingolimod in the FREEDOMS study extension, patients showed improvements in clinical and MRI outcomes, consistent with the effects observed in fingolimod-treated patients in the core study.

In addition, patients receiving continuous fingolimod treatment during the FREEDOMS core study and extension phase demonstrated sustained, low-disease activity on clinical and MRI end points in the extension phase. These patients also had better overall outcomes than patients switched from placebo to fingolimod.

In continuously treated patients, Dr. Kappos reported, the brain-volume loss benefits observed in the phase III FREEDOMS study were sustained during the extension phase, indicating a long-term effect of fingolimod for as many as four years. In patients switched from placebo to fingolimod, brain-loss benefits were observed early during the first year of active treatment.

Brain-volume loss outcomes were better in continuously treated patients than in switch patients, indicating a smaller overall loss in brain volume with earlier initiation of fingolimod treatment. The percentage of patients free of three-month confirmed disability progression at the end of the study was 74.2% in the continuous 1.25-mg dosage group, 73.9% in the continuous 0.5-mg dosage group, and 66.3% in the placebo-fingolimod switched group.

The percentage of patients free of six-month confirmed disability progression at the end of the study was 79.3% in the continuous 1.25-mg dosage group, 80% in the continuous 0.5-mg dosage group, and 72.7% in the placebo-fingolimod switched group.

Annualized relapse rates at the end of the study were 0.164 in the continuous 1.25-mg dosage group, 0.185 in the continuous 0.5-mg dosage group, and 0.357 in the placebo-fingolimod switched group.

Mean percentage of brain-volume change at the end of the study was -1.6 in the continuous 1.25-mg dosage group, -1.7 in the continuous 0.5-mg dosage group, and -2.2 in the placebo-fingolimod switched group.