Faculty Bibliography

Background: Anti-LINGO-1 is a monoclonal antibody antagonist of LINGO-1, an oligodendrocyte differentiation and myelination suppressor. Objective: To determine the efficacy/safety of anti-LINGO-1 for CNS remyelination. Methods: Subjects with a first unilateral acute optic neuritis episode were treated with high-dose steroids and randomized to 100mg/kg anti-LINGO-1 IV or placebo every 4 weeks (NCT01721161). Subject and IRB approval were obtained. Nerve conduction latency recovery using full-field visual evoked potential (FF-VEP) in the affected eye over time versus unaffected eye at baseline assessed remyelination (pre-specified primary endpoint). Between-treatment comparisons were evaluated by ANCOVA and mixed-effect model repeated measure (MMRM) in subjects who completed the study and did not miss >1 study dose or receive MS modifying therapy (prespecified per-protocol population). Safety/tolerability was evaluated in those who received >1 study dose and included adverse event (AE) and clinical laboratory result assessments. Results: Anti-LINGO-1-treated subjects (n =33) showed improved latency recovery versus placebo (n=36): mean (95% confidence interval) -7.55ms (-15.12 to 0.01) at Week 24 (P=0.05); -9.13ms (-16.11 to -2.14; P=0.01) at Week 32. 54% of anti-LINGO-1 subjects had no/mild latency delay at Week 24 (affected eye FF-VEP latency <10% worse than baseline fellow eye) versus 27% of the placebo group (P=0.036). Additional subgroup analyses will be presented. 34/41 in each group experienced any AE, serious AEs occurred in 2 placebo and 5 anti-LINGO-1 subjects, and there were 3 treatment-related serious AEs. Conclusions: Improvement in FF-VEP latency is consistent with the first evidence of remyelination in a Phase 2 trial. Anti-LINGO-1 was generally well tolerated

BACKGROUND AND PURPOSE: We examine whether the proportion of the US population with