Feast or famine in multiple sclerosis therapeutics

Despite this great progress, current multiple sclerosis treatments seem to predominantly benefit the inflammatory lesion activity that underlies relapsing multiple sclerosis, leaving the progressive aspects (ie, gradual disability worsening without clinical relapses) mostly unabated. Siponimod and ocrelizumab are two agents with regulatory approval for progressive forms of multiple sclerosis (primary progressive and secondary progressive multiple sclerosis); these drugs provide the most benefit to patients with clinical relapses or disease activity on MRI.1,2 As a result, when US and European regulators recommended approval of siponimod for secondary progressive multiple sclerosis, they restricted its use to patients with active disease. The authors selected three experimental drugs (amiloride, fluoxetine, and riluzole) for MS-SMART that were identified by extensive systematic review of 532 treatment candidates.4 These drugs target axonal pathobiology and neuroprotection, and have extensive evidence of use in humans with established safety profiles, so were ready for trial testing in progressive multiple sclerosis.