[Pubmed] Nipocalimab and other FcRn blockers in neuromuscular disorders

[RSS-Bot]

Pharmacol Ther. 2026 Jul 3:109071. doi: 10.1016/j.pharmthera.2026.109071. Online ahead of print.

ABSTRACT

Neonatal Fc receptor (FcRn) inhibition represents a novel and targeted therapeutic approach for autoimmune neuromuscular disorders driven by pathogenic IgG autoantibodies. Nipocalimab is one of those, and it is a fully human, high-affinity IgG1 monoclonal antibody that blocks FcRn-IgG interactions, thereby accelerating degradation of IgG while sparing other immunoglobulin subtypes and cellular immune responses. This selective mechanism offers clear advantages over conventional immunosuppressive and immunomodulation therapies, like intravenous immunoglobulin, plasma exchange, steroidal and nonsteroidal immunosuppressants, and B-cell-depleting agents, including rapid onset of action, reversibility, and a favorable safety profile. Clinical evidence is most robust in generalized myasthenia gravis (MG), where phase II and III randomized trials demonstrated significant, dose-dependent reductions in MG-ADL and QMG scores, rapid clinical responses, and acceptable tolerability compared to placebo. Efficacy outcomes were broadly similar with all FcRn inhibitors, including efgartigimod and rozanolixizumab, establishing FcRn blockade as an effective strategy in antibody-mediated MG. Beyond MG, ongoing studies are evaluating nipocalimab in chronic inflammatory demyelinating polyneuropathy (CIDP), while efgartigimod has already shown significant relapse-prevention benefits. In contrast, FcRn inhibition appears ineffective in multifocal motor neuropathy, likely reflecting its predominantly IgM-mediated pathophysiology. Emerging data also suggest a potential role for FcRn inhibitors in immune-mediated myopathies, particularly those driven by IgG autoantibodies, although evidence remains sparse and preliminary. Overall, FcRn inhibition-and nipocalimab in particular-offers a promising, mechanism-based treatment paradigm across a spectrum of IgG-mediated neuromuscular diseases, with ongoing trials expected to further refine its clinical role, optimal indications, and long-term safety.

PMID:42398839 | DOI:10.1016/j.pharmthera.2026.109071


Source: https://pubmed.ncbi.nlm.nih.gov/4239883 ... 6&v=2.20.0