Siponimod in the treatment of multiple sclerosis

ABSTRACT

Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated demyelinating events followed by slow progressive accumulation of disability. Over the past 2 decades, multiple medications have been studied and approved for use in MS. Most of these agents work by modulating or suppressing the peripheral immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux of lymphocytes from lymph nodes and thymus. There are promising data suggesting that it may also have a direct neuroprotective property independent of peripheral lymphocytopenia.

Areas covered: We reviewed the pharmacology and the clinical and radiological effects of siponimod.

Expert opinion: The selective effect of siponimod on the S1P1 and S1P5 receptors offers a favorable side-effect profile and transient bradycardia can be avoided by dose titration. A phase-II study showed that siponomod has dose-dependent beneficial effects in patients with relapsing remitting disease. The results of a phase-III study suggest that siponimod may be beneficial in secondary progressive MS, at least in patients with disease activity.

KEYWORDS:

• BAF-312
• multiple sclerosis
• progressive multiple sclerosis
• siponimod
• sphingosine 1 phosphate receptor

Box 1. Drug summary.

Table

Article Highlights

• Siponimod is recently approved as a next generation S1P receptor modulator for MS

• Siponimod has an oral formulation with blood-brain-barrier penetration

• The agent is designed for increased S1P receptor specificity which may limit toxicity, particularly cardiac arrhythmia concerns

• There are reported findings of efficacy in a randomized clinical trial in secondary progressive MS patients

• Controversy exists regarding the efficacy of siponimod and other drugs in progressive forms of MS

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.