FREEDOMS II
Fingolimod
FREEDOMS II independently confirmed the relapse and MRI efficacy of fingolimod 0.5 mg versus placebo.
- Phase
- Phase III
- Population
- Relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Jun 2006 — Jun 2011
What was compared
Intervention
Fingolimod 0.5 mg
Orally once daily
n=358Comparator
Placebo
Matching oral capsule once daily
n=355Additional randomized arm
Fingolimod 1.25 mg
Orally once daily; later switched to 0.5 mg by amendmentn=3701,083 randomized24 months controlled phase
Primary endpoint
Prespecified outcome
Annualized relapse rate
24 months
Outcome figure
Primary endpoint results
Intervention Comparator or reference
Annualized relapse rate
Relapses per participant-year
48% lower relapse rate; rate ratio 0.52 (95% CI 0.40–0.66; P<0.0001).
Selected secondary outcomes
Brain volume
Percentage brain-volume loss favored fingolimod.
Disability progression
The confirmatory disability endpoint was not significant.
Study population
- Randomized
- 1,083 randomized
- Age
- 18–55 years eligible
- Disability
- EDSS 0–5.5
- Disease definition
- Relapsing-remitting multiple sclerosis
Who entered the trial
Key inclusion criteria
- Relapsing-remitting multiple sclerosis
- Baseline EDSS 0–5.5
- Protocol-defined recent disease activity
Key exclusion criteria
- Major immune, malignant, pulmonary, or cardiac disease
- Pregnancy or breastfeeding
- Other protocol-defined contraindications to S1P-modulator treatment
Safety signal
- Lymphopenia, liver-enzyme elevation, herpes zoster, hypertension, first-dose bradycardia, and atrioventricular block were more frequent with fingolimod.
- Serious adverse events occurred in 15% with fingolimod 0.5 mg and 13% with placebo.
Why it mattered
FREEDOMS II confirmed that the relapse effect of fingolimod was reproducible in a separate large pivotal population.
Important limitation
The trial did not reproduce a significant disability-progression benefit, emphasizing that consistent relapse efficacy does not guarantee concordant disability results.