Understanding gMG: Autoantibodies and Life-Altering Muscle Weakness

There are several treatment options approved by the FDA for the lifelong autoantibody-driven disease, myasthenia gravis (MG): efgartigimod alfa-fcab (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo) from Argenx, eculizumab (Soliris) and ravulizumab-cwvz (Ultomiris) from Alexion Pharmaceuticals, and rozanolixizumab-noli (Rystiggo) and zilucoplan (Zilbrysq) from UCB.1

At present, the FDA is reviewing the biologics license application for nipocalimab (Johnson & Johnson), which just received a priority review designation, for use in patients who have antibody-positive generalized MG (gMG). The designation was given based on data from the phase 3 Vivacity-MG3 study (NCT04951622).2

In the first part of our discussion with Katie Abouzahr, MD, vice president, Autoantibody Diseases, and Maternal-Fetal Immunology Disease Area Leader, Johnson & Johnson Innovative Medicine, she provides background on gMG and how the disease affects patients’ long-term quality of life.

This transcript has been lightly edited for clarity.

Transcript

Can you provide an overview of gMG and its key clinical features?

It is a disease that affects the skeletal muscles. It's actually caused predominantly by antibodies that have become pathogenic—autoantibodies, as we call them. And in myasthenia [gravis], there are 3 types that account for the vast majority of all myasthenia gravis cases. The first one is an IgG1 [immunoglobulin G1] autoantibody against the acetylcholine receptor at the neuromuscular junction, AChR. The second most common type is an IgG4 [immunoglobulin G4] against muscle specific kinase, called MuSK. And then there's a rarer type LRP4 plus against lipoprotein. Between those 3, you account for maybe 95% of all myasthenia gravis cases.

So what does that do to you? It effectively impacts your skeletal muscles. You’re your skeletal muscles is not just moving your limbs. It's also opening and closing your eyes, breathing, swallowing. So you can imagine that fluctuating weakness of those muscles can have a devastating impact. The symptoms of myasthenia gravis can be very, very devastating. They can be life threatening.

Why do people get myasthenia gravis? Autoantibody-driven diseases, and the wider autoimmunity space, we don't always know what triggers it or why people get it. We think that it's probably a combination of genetic predisposition with environmental factors.

In autoantibody diseases, what happens is you have white blood cells, a subset of them called B cells that for reasons—again, we don't fully understand—instead of making antibodies that protect you against disease, for example, viruses or bacteria, these B cells start making IgG [immunoglobulin G] antibodies that attack your own body. In myasthenia gravis' case, they impact your skeletal muscles, as I mentioned, with these 3 different subtypes. What triggers the B cells to do that is poorly understood and the subject of more research at the moment.

What are the long-term implications of gMG on patients' quality of life?

So myasthenia [gravis] actually has 2 peaks: younger women and then men slightly later in life. That means that actually 1 in 5 patients with myasthenia gravis is a woman of childbearing potential. It also does have some impact in pediatric and adolescent populations, maybe 10%, 15%, depending on the data source of patients diagnosed as adolescents. That said, it can affect anybody—any race, ethnicity and gender—and at any time in life. Those are just sort of the 2 peaks, younger women and older men.

Then the progression of the disease will vary greatly by individual. But broadly speaking, you often see patients start with more localized symptoms—not always, but often—and that can be ocular myasthenia gravis, where patients may describe double vision or difficulty opening their eyes. Around 1 in 5 patients at some point will experience a myasthenia crisis, which is a medical emergency affecting the ability to breathe, and patients need to be admitted into the hospital, sometimes into intensive care. So a very severe manifestation can also present with that. And then depending again on the literature that you read, a majority, many patients will progress from more localized to generalized myasthenia gravis.

References

1. Myasthenia gravis treatments. Myasthenia Gravis Foundation of America. Accessed January 17, 2025. https://myasthenia.org/myasthenia-gravis-treatments/

2. Nipocalimab granted U.S. FDA priority review for the treatment of generalized myasthenia gravis. News release. PR Newswire/Johnson & Johnson. January 9, 2025. Accessed January 17, 2025. https://www.prnewswire.com/news-releases/nipocalimab-granted-us-fda-priority-review-for-the-treatment-of-generalized-myasthenia-gravis-302346976.html