Commentary
Video
Understanding the Therapeutic Potential of Nipocalimab: Katie Abouzahr, MD
Author(s):
The vice president, Autoantibody Portfolio and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson, provided perspective on the unique molecular structure of nipocalimab seen across nonclinical and clinical studies. [WATCH TIME: 3 minutes]
WATCH TIME: 3 minutes
"The other thing you think of with an FcRn (inhibitor) is, is it binding very specific to the Fc binding site of the FcRn? As you’ll seen, we’ve described that nipocalimab’s unique electromolecular attributes have both of these things. So, high binding affinities that are specific, and the binding affinity is pH-independent."
Myasthenia gravis (MG) is an autoantibody disease where autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signaling, and impair or prevent muscle contraction. The disease impacts an estimated 700,000 people worldwide, with 85% of these patients experiencing the more extensive form of the disease, generalized MG. Nipocalimab (Johnson & Johnson), an investigational treatment in development for MG, is designed to exclusively block binding of immunoglobulin G (IgG) to the neonatal fragment crystallizable (Fc) receptor (FcRn) resulting in decreased levels of circulating IgG, including IgG autoantibodies.
More recently, at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, investigators presented research on the key non-clinical properties and clinical outcomes of nipocalimab in gMG. Cell based assays, in vivo mouse and cynomolgus monkey studies, and human clinical data was used, with binding epitopes on FcRn determined through x-ray crystallography. All told, results showed that nipocalimab demonstrates a consistent dose-dependent pharmacokinetic-pharmacodynamic-receptor occupancy relationship in nonclinical and clinical studies leading to rapid decreases in IgG including IgG autoantibodies correlating to clinical response in gMG.
Nipocalimab remains investigational for gMG and is currently the only anti-FcRn currently being studied across the 3 segments of autoantibody diseases: maternal fetal, rare autoantibody, and prevalent rheumatology. Katie Abouzahr, MD, a study author on the research paper, sat down with NeurologyLive® following the meeting to discuss nipocalimab and the promise behind its mechanism of action. Abouzahr, vice president, Autoantibody Portfolio and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson, talked about some of its specific unique properties and how it differs from other MG agents. In addition, she discussed how the pH-independent properties of the therapy and its ability to not exert pharmacology in the fetus has allowed researchers to evaluate its potential in autoantibody driven diseases.
Click here for more coverage of AAN 2024.
