EXPAND

Siponimod

EXPAND showed that siponimod modestly delayed confirmed disability progression in secondary progressive multiple sclerosis.

Phase
Phase III
Population
Secondary progressive multiple sclerosis (SPMS)
Controlled period
Dec 20, 2012 — Apr 29, 2016

What was compared

Randomized 2:1Double-blindPlacebo-controlledEvent-driven
Intervention

Siponimod

2 mg orally once daily after dose titration

n=1,105 randomized
Comparator

Placebo

Matching oral tablet once daily

n=546
1,651 randomized; 1,645 analyzedUp to 3 years controlled phase

Primary endpoint

Prespecified outcome

3-month confirmed disability progression

Event-driven follow-up, up to 3 years

Outcome figure

Primary endpoint results

Intervention Comparator or reference

3-month confirmed disability progression

Participants with progression (%)

Event-driven follow-up, up to 3 years
Siponimod
26%
Placebo
32%

21% relative risk reduction; HR 0.79 (95% CI 0.65–0.95; P=0.013).

Selected secondary outcomes

Timed 25-foot walk

The key walking outcome did not show a significant treatment effect.

MRI

T2 lesion-volume and inflammatory lesion outcomes favored siponimod.

Study population

Randomized
1,651 randomized; 1,645 analyzed
Age
Mean 48.0 years; eligible 18–60
Sex
992 women (60%)
Disability
EDSS 3.0–6.5
Disease definition
Secondary progressive MS with progression for at least 6 months

Who entered the trial

Key inclusion criteria

  • Prior relapsing-remitting MS followed by secondary progressive disease
  • Progressive disability for at least 6 months
  • Baseline EDSS 3.0–6.5

Key exclusion criteria

  • Recent relapse or corticosteroid treatment
  • Macular edema identified during screening
  • Medically unstable condition or inability to undergo MRI

Safety signal

  • Lymphopenia, liver-enzyme elevation, bradyarrhythmia, macular edema, hypertension, zoster reactivation, and convulsions were more frequent.
  • Serious adverse events occurred in 18% with siponimod and 15% with placebo.

Why it mattered

EXPAND was the first large modern pivotal trial to show a significant disability-progression effect for an oral therapy in SPMS.

Important limitation

The absolute difference in 3-month progression was modest, the walking endpoint was negative, and eligibility selected a narrower population than the full clinical spectrum of SPMS.

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