New and emerging immune-targeted drugs for the treatment of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered.

Keywords: clinical trials; disease-modifying drugs; drug development; immunomodulatory drugs; monoclonal antibodies; neuroinflammation.

Figure 1

Kaplan–Meier estimated median age at multiple sclerosis clinical onset and at Disability Status Score (DSS) score of both 3 (n = 2054) and 6 (n = 1415) in people with MS with relapsing (blue columns) and progressive (red columns) onset. Data derived from Figure 2 of Leray et al. [89]

Figure 2

Antigen presentation stimulates naïve T cells to become either cytotoxic CD8⁺ cells or helper CD4⁺ cells. CD4⁺ and CD8⁺ are receptors that assist the binding of T cell receptors with an antigen presenting cell. The inflammatory sequelae associated with MS may be triggered by an antigen with some epitope homology with one or more myelin-associated protein