After years of a therapeutic drought in generalized myasthenia gravis (gMG), new targeted therapies are finally providing options for rapidly effective and safe treatment.
This rare autoimmune neuromuscular disease, characterized by fluctuating muscle weakness and fatigue, was typically treated with corticosteroids, broad-spectrum immunosuppressants, and intravenous immunoglobulins or plasmapheresis for myasthenia gravis crisis or severe symptoms. Rituximab (Rituxan) also has been used off-label.
“Despite our best efforts with all of our old toolbox, there are a significant number of patients who have less-than-adequate improvement in strength,” said James Howard Jr., MD, of the University of North Carolina at Chapel Hill, who has been involved in clinical trials developing complement and neonatal Fc receptor inhibitors “that started what I now consider the revolution in the management of myasthenia.”
The first of these was complement inhibitor eculizumab (Soliris), approved in 2017 as a treatment for adult gMG patients who are anti-acetylcholine receptor (AChR) antibody-positive. In the phase III REGAIN trial, eculizumab showed a trend for greater change from baseline to week 26 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score compared with placebo (P=0.0698) for adults with anti-AChR antibody-positive gMG refractory to immunosuppressive treatment based on significant unresolved disease symptoms.
Ravulizumab (Ultomiris), a drug similar to eculizumab but with a longer dosing interval, was approved for gMG in 2022, based on data from the CHAMPION study.
In 2021, a novel agent — efgartigimod (Vyvgart) — won approval for gMG in adults who test positive for the anti-acetylcholine receptor (AChR) antibody. A subcutaneous formulation gained approval in June 2023 as well. The drug is a humanized monoclonal antibody against neonatal Fc receptor to block its interaction with pathogenic immunoglobulin G (IgG) autoantibodies, reducing the circulating levels of IgG that can impair synaptic transmission at the neuromuscular joint.
In the phase III ADAPT trial of AChR antibody-positive adults with gMG, 68% of efgartigimod-treated patients had a clinically significant, at least a 2-point improvement on the 24-point MG-ADL score, compared with 30% of those receiving placebo (P