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

RandomizedDouble-blindPlacebo-controlledMulticenter
Intervention

Fingolimod 0.5 mg

Orally once daily

Comparator

Placebo

Matching oral capsule once daily

Additional randomized arm

Fingolimod 1.25 mg

Orally once daily
1,272 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

24 months
Fingolimod 0.5 mg
0.18
Fingolimod 1.25 mg
0.16
Placebo
0.40

Both doses reduced relapse rate versus placebo (P<0.001).

Selected secondary outcomes

3-month confirmed disability progression

17.7% with 0.5 mg versus 24.1% with placebo; HR 0.70 (P=0.02).

MRI activity

Both doses were superior to placebo across prespecified MRI measures.

Study population

Randomized
1,272 randomized
Age
18–55 years eligible
Sex
889 women (70%)
Disability
EDSS 0–5.5
Disease definition
Relapsing-remitting MS with recent clinical activity

Who entered the trial

Key inclusion criteria

  • Relapsing-remitting multiple sclerosis
  • At least one relapse in 1 year or two relapses in 2 years
  • Baseline EDSS 0–5.5

Key exclusion criteria

  • Other major immune, malignant, pulmonary, or cardiac disease
  • Pregnancy or breastfeeding
  • Other protocol-defined safety conditions affecting S1P-modulator treatment

Safety signal

  • Bradycardia and atrioventricular conduction block occurred at treatment initiation.
  • Macular edema, elevated liver enzymes, and mild hypertension contributed to adverse events and discontinuation.

Why it mattered

FREEDOMS was central to establishing the first oral S1P-receptor modulator as an effective disease-modifying therapy.

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.

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