TRANSFORMS

Fingolimod

TRANSFORMS directly compared oral fingolimod with intramuscular interferon beta-1a and showed superior control of relapses over 1 year.

Phase
Phase III
Population
Relapsing-remitting multiple sclerosis (RRMS)
Controlled period
May 2006 — Sep 2008

What was compared

RandomizedDouble-blindDouble-dummyActive-controlled
Intervention

Fingolimod 0.5 mg

Orally once daily

Comparator

Interferon beta-1a

30 μg intramuscularly once weekly

Additional randomized arm

Fingolimod 1.25 mg

Orally once daily
1,292 randomized12 months controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

12 months

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

12 months
Fingolimod 0.5 mg
0.16
Fingolimod 1.25 mg
0.20
Interferon beta-1a
0.33

Both fingolimod doses were superior to interferon beta-1a (P<0.001).

Selected secondary outcomes

MRI lesions

New or enlarged T2 lesions favored both fingolimod doses.

Disability progression

No significant difference among groups during the 1-year core.

Study population

Randomized
1,292 randomized
Age
18–55 years eligible
Disability
EDSS 0–5.5
Disease definition
Relapsing-remitting MS with recent relapse activity

Who entered the trial

Key inclusion criteria

  • Relapsing-remitting multiple sclerosis
  • Recent history of at least one relapse
  • Baseline EDSS 0–5.5

Key exclusion criteria

  • Inability to tolerate interferon beta-1a
  • Major immune, malignant, pulmonary, or cardiac disease
  • Pregnancy or breastfeeding

Safety signal

  • Fingolimod-associated events included bradyarrhythmia, macular edema, hypertension, herpesvirus infections, and liver-enzyme elevation.
  • Two fatal infections occurred in the 1.25 mg group.

Why it mattered

It was a pivotal active-comparator demonstration that an oral therapy could outperform a widely used injectable therapy on relapse and MRI outcomes.

Important limitation

The controlled comparison lasted only 1 year and did not demonstrate a disability-progression difference. The registry’s later completion date includes extension follow-up.

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