Ponesimod for the treatment of relapsing multiple sclerosis

ABSTRACT

Introduction

Multiple Sclerosis (MS) is an immune-mediated, complex, chronic inflammatory, and neurodegenerative disease of the central nervous system. Among the several therapeutic options developed over the last decade for relapsing MS (RMS), fingolimod, a sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral treatment. The adverse events associated with fingolimod have limited its use in certain populations, thus further stimulating the search for other S1PR modulators.

Areas covered

The authors reviewed the English-published literature on ponesimod using the PubMed database. The search terms used were ‘ponesimod’ or ‘ACT-128,800’ and ‘multiple sclerosis.’ Available data on the pharmacological profile of ponesimod and the information on clinical efficacy and safety drawn from clinical trials in comparison with other S1PR modulators are presented and discussed.

Expert opinion

Published peer-reviewed data on long-term safety and efficacy are still lacking but have been collected and regulatory authorities expressed a favorable opinion to market access. At present, we believe that ponesimod has little chance of becoming a leading treatment for RMS due to the availability of many alternative options and the timing of market access. Given its favorable risk-benefit and convenience profile, however, ponesimod might become a leading option among S1P receptor modulators used for RMS.

KEYWORDS:

• ACT-128,800
• disease-modifying therapies
• multiple sclerosis
• ponesimod
• sphingosine-1-phosphate modulator
• risk-benefit
• efficacy
• safety
• tolerability

Article highlights

• Ponesimod is a highly selective, second-generation, orally active and rapidly reversible modulator of the sphingosine-1-phosphate receptor 1 (S1P1).

• Gradual up-titration of ponesimod could mitigate first-dose effects and facilitate its use over fingolimod without requiring pharmacogenetic investigations contrary to siponimod

• Ponesimod determines a dose-dependent sequestration of lymphocytes in lymphoid organs leading to a decrease in peripheral blood lymphocyte count.

• Ponesimod is eliminated within 1 week of stopping treatment, thus allowing rapid reversibility of its effects.

• The rapid reversibility of effects on the immune system is relevant in several clinical situations, e.g. infections, vaccinations, DMD sequencing and will favour the choice of ponesimod over other S1PR modulators by neurologists.

• Timing of market access and pricing will impact on the market share of ponesimod

Declaration of interest

A Lugaresi has received speaker’s honoraria, travel expenses, or grants from Biogen Idec, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme, and Teva Pharmaceuticals. E Baldin, meanwhile, has received travel grants from Biogen Idec, Roche, and Sanofi/Genzyme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares having worked on the OPTIMUM study, served on the steering committee for the same, and accepted consulting honoraria from Janssen and Actelion. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.