FcRn Inhibitors and Emerging Therapies Reshape Myasthenia Gravis Treatment Landscape

Three drugs that inhibit the immunoglobulin G (IgG) neonatal fragment crystallizable receptor (FcRn) have been approved to treat generalized myasthenia gravis (MG) in recent years: efgartigimod (Vyvgart), rozanolixizumab (Rystiggo), and nipocalimab (Imaavy). Two of these agents — efgartigimod and nipocalimab — will face a direct comparison in the open-label EPIC trial, which has a primary outcome of mean percent change from baseline in total IgG levels over weeks 8, 10, and 12.

"Despite dramatic recent advances in generalized myasthenia gravis, many patients still experience fluctuating symptoms and incomplete symptom control," noted a Stanford University clinician. "The EPIC study will be the first head-to-head trial comparing two FcRn blockers, giving clinicians direct evidence on the relative efficacy and safety of these novel therapies rather than relying on cross-trial comparisons."

FcRn inhibitors are part of a complex set of treatment options for generalized MG that include pyridostigmine, corticosteroids, azathioprine and other oral immune suppressants, thymectomy, rescue therapies including plasma exchange and intravenous immunoglobulin (IVIG), B-cell depleting agents (particularly rituximab), and complement inhibition. Despite this array of options, there remains a substantial unmet need in the treatment of MG. Although 70% to 80% respond to initial treatment, MG patients often depend on maintenance treatment to keep their disease in remission. Side effects associated with steroids and immunosuppressive therapy can accumulate over time and increase morbidity and mortality. In addition, about 15% of MG patients have treatment-refractory disease.

FcRn is a subtype of receptor for the IgG Fc domain that protects IgG molecules bound to it from lysosomal destruction. By blocking FcRn, inhibitors reduce circulating IgG, including the autoantibodies that drive disease activity. FcRn antagonists may prove useful in several treatment roles in MG, including as a bridge treatment around thymectomy or to using nonsteroidal immune suppressants. They also may be an add-on for refractory disease, or monotherapy for those unresponsive to other treatment. Because FcRn inhibitors elicit transient reduction in IgG levels, vaccination with live-attenuated or live vaccines shortly before, during, or shortly after the infusion series is not recommended.

Data from recent MG trials presented at AAN 2026 reflected an expansion of therapeutic targets and treatment paradigms. The phase 3 RemeMG trial is evaluating the upstream B-cell modulator telitacicept. In complement inhibition, the phase 3 PREVAIL trial showed the subcutaneously self-administered gefurulimab met its primary endpoint. A significant conceptual shift is emerging from chimeric antigen receptor T-cell therapies, where the phase 2 KYSA-6 study of KYV-101 demonstrated robust improvements in MG-ADL and QMG scores. Critically, some patients in the KYV-101 study successfully discontinued background immunotherapy, suggesting that treatment-free remission is a feasible goal. These findings indicate a potential move from chronic disease suppression toward achieving a durable immune system reset.

Immunovant's FcRn blocker batoclimab failed to show efficacy in a pair of phase 3 trials for thyroid eye disease (TED), missing its primary efficacy objective in both the GO-1 and GO-2 studies. The company is now focusing its resources on IMVT-1402, a follow-up FcRn blocker. Batoclimab had shown efficacy in MG, but Immunovant opted not to take that indication further in order to focus on IMVT-1402, which offers similarly potent reductions in IgG without affecting levels of albumin and LDL cholesterol. Immunovant is also running studies of IMVT-1402 in a range of other autoimmune conditions, including MG, chronic inflammatory demyelinating polyneuropathy (CIDP), Sjögren's disease (SjD), and cutaneous lupus erythematosus (CLE).