Oral ponesimod in relapsing–remitting MS: a randomised phase II trial

Treatment, therapies and management:
This double-blind, placebo-controlled, phase II study evaluated the efficacy and safety of ponesimod for the treatment of patients with relapsing–remitting multiple sclerosis (RRMS). Ponesimod is a reversible, orally active, selective sphingosine-1-phosphate (S1P) receptor modulator. Binding of ponesimod to the S1P1 receptor results in a lymphocyte sequestration in the lymph nodes.

In this study, 464 patients were randomised to receive once-daily oral ponesimod 10, 20 or 40 mg, or placebo for 24 weeks. The primary endpoint was the cumulative number of new T1 gadolinium-enhanced (T1 Gd+) lesions. Secondary endpoints were the annualised confirmed relapse rate (ARR) and time to first confirmed relapse. Safety and tolerability were also evaluated.

The mean cumulative number of new T1 Gd+ lesions at weeks 12–24 was significantly lower in the ponesimod 10 mg, 20 mg and 40 mg groups compared with placebo. The mean ARR was lower with 40 mg ponesimod versus placebo. Frequently reported adverse events (AEs), with a higher incidence in the three ponesimod groups compared with placebo, were anxiety, dizziness, dyspnoea, increased alanine aminotransferase, influenza, insomnia and peripheral oedema.

Ponesimod was associated with first-dose cardiac effects, similarly to other S1P receptor modulators such as fingolimod. Ponesimod was generally well tolerated at doses of 10 and 20 mg; the 40 mg dose showed signs of reduced tolerability with no additional benefit with respect to MRI or pharmacodynamics efficacy compared with the 20 mg dose.

Authors: Olsson T, Boster A.
Source: J Neurol Neurosurg Psychiatry. 2014 Apr 8. doi: 10.1136/jnnp-2013-307282. [Epub ahead of print]
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