OPTIMUM

Ponesimod

OPTIMUM was the first phase III trial to compare two oral MS therapies directly, showing superior relapse and MRI control with ponesimod versus teriflunomide.

Phase
Phase III
Population
Relapsing multiple sclerosis (RMS)
Controlled period
Jun 4, 2015 — May 16, 2019

What was compared

Randomized 1:1Double-blindDouble-dummyOral active comparator
Intervention

Ponesimod

20 mg orally once daily after 14-day up-titration

n=567
Comparator

Teriflunomide

14 mg orally once daily

n=566
1,133 randomized participants108 weeks controlled phase

Primary endpoint

Prespecified outcome

Annualized relapse rate

108 weeks

Outcome figure

Primary endpoint results

Intervention Comparator or reference

Annualized relapse rate

Relapses per participant-year

108 weeks
Ponesimod
0.202
Teriflunomide
0.290

30.5% relative rate reduction with ponesimod (P<0.001).

Selected secondary outcomes

Combined unique active MRI lesions

56% lower with ponesimod (1.405 versus 3.164 per year; P<0.001).

Confirmed disability accumulation

12- and 24-week disability outcomes did not differ significantly.

Study population

Randomized
1,133 randomized participants
Age
Mean 36.7 years; range 18–55
Sex
735 women (64.9%)
Disability
EDSS 0–5.5
Disease definition
Relapsing MS with recent clinical or MRI activity

Who entered the trial

Key inclusion criteria

  • Defined based on McDonald criteria 2010
  • Recent clinical attack or gadolinium-enhancing MRI activity
  • Ambulatory, with EDSS no higher than 5.5

Key exclusion criteria

  • Clinically important cardiovascular, pulmonary, immune, hepatic, or ophthalmic conditions
  • Pregnancy or breastfeeding
  • MRI contraindication or another condition creating unacceptable study risk

Safety signal

  • Treatment-emergent and serious adverse-event rates were similar between groups.
  • Adverse-event discontinuation was more frequent with ponesimod: 8.7% versus 6.0%.

Why it mattered

OPTIMUM moved pivotal evidence beyond placebo and injectable comparisons by directly testing two contemporary oral therapies.

Important limitation

Superiority was demonstrated for relapse, fatigue, and MRI outcomes—not for confirmed disability accumulation during the controlled period.

Suggest an update