Fingolimod: Long-Term (up to 4 Years) Efficacy in Relapsing-Remitting Multiple Sclerosis Patients in Freedoms and Freedoms II Study Extensions

Background: In the 24-month (M) FREEDOMS and FREEDOMS II core studies, oral, once-daily fingolimod (0.5 mg or 1.25 mg) showed beneficial effects on clinical and MRI endpoints vs placebo (PBO) in patients (pts) with relapsing-remitting multiple sclerosis.

Objectives: To report long-term (up to 4 years [y]) efficacy outcomes of fingolimod in the FREEDOMS and FREEDOMS II extension studies.

Methods: Pts treated with fingolimod (0.5 mg or 1.25 mg) in the core studies (M 0-24) continued the same dose (continuous group) in the extension studies, while those on PBO were rerandomized (1:1) to fingolimod (0.5 mg/1.25 mg; switch group). After study amendment, all pts received open-label fingolimod 0.5 mg until end of study (EOS). Comparisons were analyzed for continuously-treated groups vs the merged 0.5 mg/1.25 mg switch group.

Results: Of 1272 pts randomized in the FREEDOMS core study, 920 (72.3%) entered the extension and of these 773 (84.0%) pts completed the study. In the core ITT, from M 0-EOS, the annualized relapse rate (ARR) remained significantly lower in the continuous fingolimod groups (1.25 mg, 0.16; 0.5 mg, 0.19) vs the switch group (0.36, both P<0.001). In the extension ITT, pts who switched from PBO to fingolimod had a 55% reduction in ARR (0.13 vs 0.29 during the core phase, respectively; P<0.001). MRI measures continued to show significantly reduced brain atrophy in the continuous fingolimod 0.5 and 1.25 mg groups vs the switch group (mean % change in brain volume -–1.67% and –1.64% vs –2.24%; both P≤0.001) at EOS. Of 1083 pts randomized in the FREEDOMS II study, 632 (58.4%) entered the extension and of these 529 (83.7%) pts completed the study. From M 0-EOS, the ARR remained significantly lower in the continuous fingolimod groups (0.5 mg: 0.19; 1.25 mg: 0.18) vs the switch group (0.36), resulting in relative reductions of 47% and 50% (both P<0.001). MRI measures continued to show significantly reduced brain atrophy in the continuous fingolimod groups (0.5 mg: –0.98%, 1.25 mg: –0.84%; both P≤0.002) vs the switch group (–1.33%) at EOS. Within-group comparisons will be presented for both studies.

Conclusions: Results from FREEDOMS and FREEDOMS II extension studies support long-term efficacy of fingolimod. In both studies, continuous fingolimod treatment maintained the low clinical and MRI disease activity seen in the core studies for up to 4 y. Benefits were also seen relative to core study results in pts switched from PBO to fingolimod.