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Efficacy for remyelination and safety of anti-lingo-1 monoclonal antibody (biib033) in acute optic neuritis: results from the renew study

      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 (pre-specified 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.