This work was done and completed years ago and the take home message is that the results weren’t good enough of it to be developed. Lingo-1 is part of the pathway that prevents nerve regeneration , but it was also reported to inhibit remyelination. In early trials that was dose ranging dosing up to 100mg/kg….Why do this mega dose? Well because to promote remyelination you need to get the drug into the brain and opinumab is an antibody and is 99.9% of the antibody is excluded from the brain. At this point I say no more as you are climbing a hill before get anywhere. In another trial they noted “U-shaped dose response to opicinumab with more favourable outcomes in the 10- and 30 mg/kg groups” to me it just says why it didnt work. In the currenty study they used a fixed dose of 750mg so that is about 10-15mg/kg every month. It concludes that maybe a different dose could be used and outcomes measurements could be improved..Say not more as you have heard this before
Calabresi PA, Giovannoni G, Hartung HP, Naismith RT, Fox RJ, Sormani MP, Arnold DL, Kappos L, Valis M, Newsome SD, Belkin MI, Bartholomé E, Riester K, Javor A, Lyons J, Bradley DP, Fisher E, Tagge I, Naylor ML, Belachew S, Deykin A, Franchimont N, Zhu B, Cheng W. Safety and efficacy of opicinumab in participants with relapsing multiple sclerosis (AFFINITY Part 1): A randomized, controlled, phase 2 trial. Mult Scler. 2025 Dec 26:13524585251396433. doi: 10.1177/13524585251396433.
Background: Opicinumab, a human monoclonal antibody against LINGO-1, is hypothesized to promote remyelination by enhancing the differentiation of oligodendrocyte progenitor cells.
Objective: The objective of the study is to investigate the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory disease-modifying therapies (DMTs) in participants with relapsing multiple sclerosis (RMS).
Methods: Participants with RMS aged 18-58 years, with disease duration up to 20 years, were randomized 1:1 to receive intravenous infusions of placebo or opicinumab every 4 weeks for 72 weeks. Primary endpoint was Overall Disability Response Score (ODRS) over 72 weeks.
Results: The study enrolled 263 participants. Adjusted mean difference (95% confidence interval (CI)) on ODRS was 0.15 (-0.05 to 0.35; p = 0.148) over 72 weeks, favoring opicinumab versus placebo. Numerically larger differences in favor of opicinumab were observed in participants aged ⩾ 40 years with Expanded Disability Status Scale ⩾ 3.0, with disease duration ⩾ 6 years, and receiving dimethyl fumarate as the background DMT. 85% participants in placebo group and 86% in opicinumab group had adverse events.
Conclusion: Although the AFFINITY study did not show significant difference in mean ODRS between opicinumab and placebo groups, data from AFFINITY interpreted with the previous SYNERGY study may inform the design of future remyelination trials.
Source: multiple-sclerosis-research.org