Investigational immunosuppressants in early-stage clinical trials for the treatment of multiple sclerosis

ABSTRACT

Introduction: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale.

Areas covered: The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including seven monoclonal antibodies and five small molecules.

Expert opinion: Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clinical trials of immunosuppressants for progressive MS are largely lacking.

KEYWORDS:

• Multiple sclerosis
• immunosuppressant
• experimental drug
• clinical trial
• sphingosine 1-phosphate modulator
• monoclonal antibody
• B-cell therapy

Article highlights

• Multiple sclerosis is a chronic immune mediated disease of the central nervous system for which several immunotherapies are available.

• Disease-modifying treatments for multiple sclerosis have either limited efficacy or potentially serious adverse events.

• Ongoing or recently completed clinical trials investigating twelve different immunosuppressive drugs for MS are here reviewed according to mechanism of action.

• Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with active relapsing disease.

• Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs.

• Clinical trials of immunosuppressants for progressive MS are largely lacking.

Declaration of Interest

A. Gajofatto receives research support from Merck Serono and Fondazione Cariverona. 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.

A reviewer on this manuscript has disclosed receipt of personal compensation for consulting for Adamas, Celgene, Novartis, and Pendopharm, and as a Co-Editor of Multiple Sclerosis Journal—Experimental, Translational and Clinical.

Additional information

Funding

This paper was not funded.