First phase 3 study compares two oral DMTs in RMS disease

Multiple sclerosis

By Mardi Chapman

30 Mar 2021

The selective sphingosine-1-phosphate receptor 1 (S1P1) ponesimod is superior to teriflunomide in the treatment of relapsing MS, according to the first RCT comparing two oral disease modifying treatments.

A phase 3 study comprising 1,133 adult patients from 28 countries compared 20mg daily of the oral ponesimod with 14mg daily of oral teriflunomide over 108 weeks.

The study, published in JAMA Neurology, found the primary end point – the annualised relapse rate (ARR) – favoured ponesimod.

“Ponesimod reduced ARR by 30.5% compared with teriflunomide (mean ARR, 0.202 vs 0.290; rate ratio, 0.695 [99% confidence limits (CLs), 0.536-0.902]; p < 0.001),” the study said.

Fatigue was lower in ponesimod-treated patients according to the Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ– RMS) and there were fewer combined unique active lesions (CUALs) on MRI at 108 weeks.

Confirmed disability accumulation (CDA) was similar in both groups at 12 and 24 weeks.

In an exploratory outcome, brain volume loss from baseline to week 108 was lower in the ponesimod group compared to the teriflunomide group.

As well, the odds ratio for achieving 2-year no evidence of disease activity (NEDA) in the ponesimod group compared to teriflunomide was 1.70 for NEDA-3 and 1.85 for NEDA-4.

The proportions of patients who experienced at least one treatment-emergent serious adverse event were similar in both treatment arms (8.7% v 8.1%) however TEAEs leading to treatment discontinuation were more frequent in the ponesimod group (8.7% v 6.0%).

The study said the combined effect of ponesimod on fatigue and the reduction of brain volume loss, shown against a drug with an established effect on brain volume loss, suggested ponesimod’s benefits extend to the prevention of tissue damage accumulation.

“In accordance with ponesimod’s effects on the individual outcome measures, a higher proportion of patients receiving ponesimod remained free of disease activity, both after applying the three established criteria for NEDA-3 (no relapse, no confirmed disease worsening, and no new or enlarging MRI lesions) and after adding the criterion of no brain volume change in excess of the upper limit obtained in healthy controls (NEDA-4).”

The study concluded that ponesimod in RMS was superior to the approved oral DMT teriflunomide.

The OPTIMUM study was supported by Actelion Pharmaceuticals, part of Janssen Pharmaceutical Companies.

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