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
Fingolimod 0.5 mg
Orally once daily
Interferon beta-1a
30 μg intramuscularly once weekly
Additional randomized arm
Fingolimod 1.25 mg
Orally once dailyPrimary endpoint
Annualized relapse rate
12 months
Primary endpoint results
Annualized relapse rate
Relapses per participant-year
Both fingolimod doses were superior to interferon beta-1a (P<0.001).
Selected secondary outcomes
New or enlarged T2 lesions favored both fingolimod doses.
No significant difference among groups during the 1-year core.
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 or macular edema
- Immune suppression or clinically significant coexisting systemic disease
Participants at baseline
| Characteristic | Fingolimod 0.5 mgN=431 | Fingolimod 1.25 mgN=426 | IFNβ-1aN=435 |
|---|---|---|---|
| Age, years — mean ± SD | 36.7 ± 8.8 | 35.8 ± 8.4 | 36.0 ± 8.3 |
| Female sex — n (%) | 282 (65.4%) | 293 (68.8%) | 295 (67.8%) |
| Time since MS symptom onset, years — mean ± SD | 7.5 ± 6.2 | 7.3 ± 6.0 | 7.4 ± 6.3 |
| EDSS — mean ± SD | 2.24 ± 1.33 | 2.21 ± 1.31 | 2.19 ± 1.26 |
| Relapses in previous 12 months — mean ± SD | 1.5 ± 1.2 | 1.5 ± 0.9 | 1.5 ± 0.8 |
| Previous MS therapy — n (%) | 238 (55.2%) | 249 (58.5%) | 245 (56.3%) |
| No gadolinium-enhancing lesions — n/N (%) | 288/427 (67.4%) | 270/412 (65.5%) | 268/425 (63.1%) |
SD: standard deviation; EDSS: Expanded Disability Status Scale; IFNβ: interferon beta.
Source: Cohen et al., NEJM 2010, Table 1
Safety signal
- Fingolimod-associated events included bradyarrhythmia, macular edema, hypertension, herpesvirus infections, and liver-enzyme elevation.
- Two fatal infections occurred with fingolimod 1.25 mg: disseminated primary varicella-zoster infection and herpes simplex encephalitis.
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
TRANSFORMS showed that oral fingolimod reduced relapses and MRI activity more than weekly intramuscular interferon beta-1a. The active-comparator design helped clinicians assess a new oral treatment against an established injectable option; the one-year disability result was not conclusive.
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.