Myasthenia gravis - Emerging treatments

Rozanolixizumab

Rozanolixizumab is a humanized immunoglobulin (Ig) G4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn). It is approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of generalized MG in adults who have antibodies to either acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK). In a randomized, double-blind, placebo-controlled, adaptive phase 3 study, rozanolixizumab was associated with statistically significant and clinically meaningful improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) score (which assesses signs or symptoms that are typically affected in generalized MG) and Quantitative Myasthenia Gravis (QMG) score (which assesses muscle weakness).[142] Rozanolixizumab was generally well tolerated. Further studies are ongoing.[143][144]

Zilucoplan

Zilucoplan (a macrocyclic peptide inhibitor of complement component C5) is approved by the FDA and the EMA for the treatment of generalized MG in adult patients with AChR antibodies. Rapid, meaningful, and sustained improvements in MG-ADL and QMG scores over 12 weeks were reported with zilucoplan treatment in a randomized, double-blind, placebo-controlled, multicenter phase 3 trial in a broad population of patients with mild to severe AChR-antibody-positive generalized MG.[145]

Amifampridine

The FDA granted orphan drug designation to amifampridine for the symptomatic treatment of MG in 2017. One small phase 2b, randomized, double-blind, placebo-controlled, double crossover study reported that amifampridine was safe and effective in treating muscle-specific tyrosine kinase (MuSK) MG.[146]

Belimumab

A monoclonal antibody that binds to and inhibits B-cell activating factor (BAFF, which promotes B-cell maturation and stimulation, and is present in serum and thymus of patients with MG). Belimumab did not significantly improve Quantitative Myasthenia Gravis (QMG) score compared with placebo in a phase 2 trial of patients with generalized MG, but the trial had several methodological flaws that prevented full assessment.[128][147]

Other drugs

Other drugs at early stages of investigation include nipocalimab and RVT-1401 (monoclonal antibodies that bind to FcRn); and iscalimab and bortezomib (anti-B-cell therapies).[128]

Subcutaneous immune globulin

Preliminary studies suggest that subcutaneous immune globulin as maintenance may improve functional disability in patients with MG. Reported adverse effects were local and mild.[148]

Stem-cell therapy

Case reports suggest that autologous hematopoietic stem-cell transplantation may be of benefit to some patients with refractory MG and severe or life-threatening symptoms.[149][150][151]