BG-12 and its potential for the prevention of relapse in multiple sclerosis

摘要

Abstract: Multiple sclerosis (MS) arises from an immune attack on the central nervous system producing demyelination and axonal loss. Clinically the relapsing–remitting course is characterized by subacute onset of neurological symptoms usually with partial or complete recovery, while the progressive course, predominant in the later stages, is characterized by progressive disability in the absence of relapses. A number of disease-modifying treatments have been developed and are increasingly effective at targeting relapses. Early injectable therapies such as interferon and glatiramer acetate are only partially effective, but have a good safety record. Recently, natalizumab, an intravenous therapy, demonstrated increased effectiveness, but side effects complicate its use. The first oral therapy offering good efficacy and convenience, fingolimod, was approved in USA in 2010 and Europe in 2011. BG-12 is a potential novel oral therapy for MS, which has previously been used as a different formulation for psoriasis. It has anti-inflammatory and neuroprotective actions in vitro, which makes it a promising candidate for future therapies. Phase II studies showed that BG-12 reduced MRI inflammatory activity over placebo, which was confirmed in two Phase III studies indicating immune modulation may be its principal action rather than neuroprotection. In these studies, BG-12 reduced relapse rates consistently with variable effects on progression and few serious adverse events. With its favorable efficacy–tolerability profile, BG-12 could offer a substantial step forward for the care for subjects affected by relapsing MS.