Novel therapeutic options for multiple sclerosis

Abstract

Multiple sclerosis (MS) is considered as an autoimmune disorder of the CNS with neuro-inflammatory and neurodegenerative components. We review here the innovative drugs recently registered and those in clinical development for MS. Immunomodulation has been the preferred therapeutic approach for MS since the first IFN-β was registered in the 1990s. Several immunomodulators are now available, which show a high efficacy in reducing the number of relapses in patients with the relapsing–remitting form of MS (RRMS). The high efficacy of most immunomodulators is, however, associated with substantial safety risks, notably concerning infections or cancers. Recently oral drugs have been approved for RRMS; however, biologics, and notably, monoclonal antibodies are still well represented in the development pipelines. An unmet medical need remains the treatment of the primary and secondary forms of MS or chronic progressive MS (CPMS). Half a dozen immunomodulators with proven efficacy in RRMS are now undergoing evaluation in Phase III trials in the CPMS indication. Neuroprotective drugs that prevent demyelination and/or improve remyelination would be interesting for CPMS, but these drugs are currently in the early development phase and their efficacy has not been demonstrated yet.

Keywords::

• immunomodulator
• monoclonal antibody
• multiple sclerosis
• neuroprotection
• relapse rate
• safety risk

Financial & competing interests disclosure

F Curtin is an employee and shareholder of GeNeuro. H Hartung received, with approval of the Rector of Heinrich-Heine-University, fees for consulting and speaking from Bayer Healthcare, Biogen Idec, Genzyme, GeNeuro, Merck Serono, Novartis, Roche, Sanofi and Teva. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The majority of drugs in development are immunomodulators and are mainly indicated for the relapsing–remitting form of multiple sclerosis (MS).

• Immunomodulators despite high selectivity may be associated with safety risks in particular over the long term.

• Finding efficacious molecules with a benefit: risk ratio acceptable for chronic treatment remains a formidable challenge.

• There are no treatments currently approved for patients with chronic progressive MS.

• Assessing the efficacy in chronic progressive MS indication is made difficult by the long duration of the follow-up needed and by the relative lack of responsiveness of accepted endpoints.

• Neuroprotective treatments with potential in chronic progressive forms of MS have not yet passed the clinical proof of concept stage.

• Currently there is a lack of experience with combination therapies.