FREEDOMS
Fingolimod
FREEDOMS demonstrated that once-daily oral fingolimod reduced relapses, disability progression, and MRI activity versus placebo.
- Phase
- Phase III
- Population
- Relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Jan 2006 — Jul 2009
What was compared
Fingolimod 0.5 mg
Orally once daily
Placebo
Matching oral capsule once daily
Additional randomized arm
Fingolimod 1.25 mg
Orally once dailyPrimary endpoint
Annualized relapse rate
24 months
Primary endpoint results
Annualized relapse rate
Relapses per participant-year
Both doses reduced relapse rate versus placebo (P<0.001).
Selected secondary outcomes
17.7% with 0.5 mg versus 24.1% with placebo; HR 0.70 (P=0.02).
Both doses were superior to placebo across prespecified MRI measures.
Who was studied
Key inclusion criteria
- Age 18–55 years
- RRMS diagnosis based on McDonald criteria 2005
- Baseline EDSS 0–5.5
- At least 1 relapse in the previous year or at least 2 in the previous 2 years
Key exclusion criteria
- Relapse or corticosteroid treatment in the previous 30 days
- Active infection, macular edema, or diabetes mellitus
- Immune suppression or clinically significant systemic disease
- Interferon or glatiramer acetate within 3 months before randomization
Participants at baseline
| Characteristic | Fingolimod 0.5 mgN=425 | Fingolimod 1.25 mgN=429 | PlaceboN=418 |
|---|---|---|---|
| Age, years — mean ± SD | 36.6 ± 8.8 | 37.4 ± 8.9 | 37.2 ± 8.6 |
| Female sex — n (%) | 296 (69.6%) | 295 (68.8%) | 298 (71.3%) |
| Time since MS symptom onset, years — mean ± SD | 8.0 ± 6.6 | 8.4 ± 6.9 | 8.1 ± 6.4 |
| EDSS — mean ± SD | 2.3 ± 1.3 | 2.4 ± 1.4 | 2.5 ± 1.3 |
| Relapses in previous 12 months — mean ± SD | 1.5 ± 0.8 | 1.5 ± 0.8 | 1.4 ± 0.7 |
| No previous DMT — n (%) | 244 (57.4%) | 259 (60.4%) | 249 (59.6%) |
| No gadolinium-enhancing lesions — n/N (%) | 263/424 (62.0%) | 257/424 (60.6%) | 262/416 (63.0%) |
SD: standard deviation; EDSS: Expanded Disability Status Scale; DMT: disease-modifying therapy.
Source: Kappos et al., NEJM 2010, Table 1
Safety signal
- Bradycardia and atrioventricular conduction block occurred at treatment initiation.
- Macular edema, elevated liver enzymes, and mild hypertension were reported with fingolimod and, in some cases, led to treatment discontinuation.
Later safety context
Later FDA warning (2018): severe worsening of disability was reported after fingolimod discontinuation. This post-marketing finding is separate from the controlled-trial safety results above.
FDA, Gilenya label, 2018, section 5.9 ↗Why it mattered
FREEDOMS provided pivotal placebo-controlled evidence that an oral S1P-receptor modulator could reduce relapses and confirmed disability progression. It helped move MS treatment beyond injections, while showing why initiation and organ-specific safety monitoring mattered.
Important limitation
Two doses were tested, but only 0.5 mg became the standard MS dose; longer observation was needed to define infrequent and cumulative risks.