Nipocalimab for myasthenia gravis

Last updated Sept. 5, 2024, by Lindsey Shapiro, PhD
Fact-checked by Joana Carvalho, PhD

What is nipocalimab for myasthenia gravis?

Nipocalimab, previously known as M281, is an experimental antibody therapy being developed for generalized myasthenia gravis (gMG) and other autoimmune diseases. Delivered via infusions given directly into the bloodstream (intravenously), the treatment is designed to lower the levels of the self-reactive antibodies that drive the disease.

It is currently being developed by Johnson & Johnson, which acquired nipocalimab’s original developer Momenta Pharmaceuticals in 2020.

Nipocalimab has been granted fast track and orphan drug designations from the U.S. Food and Drug Administration for gMG. Both statuses offer various financial incentives and regulatory support to help accelerate its development.

Johnson & Johnson recently submitted an application to the FDA requesting the approval of nipocalimab for gMG patients who are positive for the most common types of MG-causing self-reactive antibodies.

In addition to gMG, nipocalimab is being developed for seven other inflammatory conditions, including lupus, Sjögren’s disease, rheumatoid arthritis, chronic inflammatory demyelinating polyneuropathy, hemolytic disease of the fetus and newborn, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathy.

Therapy snapshot

How does nipocalimab work in myasthenia gravis?

An autoimmune disease, myasthenia gravis (MG) is characterized by the immune system’s mistaken attacks on the neuromuscular junction, which is the site where nerve and muscle cells communicate to coordinate voluntary movements. These attacks are driven by self-reactive antibodies, or autoantibodies, that target proteins important for neuromuscular function, most commonly acetylcholine receptors (AChRs).

MG-causing autoantibodies belong to a class of antibodies called immunoglobulin G (IgG). Normally, a protein called neonatal Fc receptor (FcRn) binds to IgG antibodies circulating in the bloodstream and helps prevent them from being degraded.

Nipocalimab is an antibody that’s designed to block the site on FcRn to which IgGs normally bind, thereby preventing their interaction. In doing so, the treatment works to accelerate the rate at which IgGs are degraded, including the harmful ones that cause gMG. By lowering the levels of MG-causing autoantibodies in the bloodstream, nipocalimab is expected to ease MG symptoms and overall disease severity.

How will nipocalimab be administered in myasthenia gravis?

In clinical trials, nipocalimab is being administered as intravenous infusions at various dosing regimens. In a Phase 3 trial involving adults with gMG, the investigational therapy is being given at a dose of 15 mg/kg once every two weeks after an initial 30 mg/kg loading dose.

Nipocalimab in myasthenia gravis clinical trials

The safety and efficacy of nipocalimab for gMG was first demonstrated in the Phase 2 Vivacity-MG study (NCT03772587). Two ongoing clinical trials are now seeking to confirm the therapy’s benefits in gMG patients: the Phase 3 Vivacity-MG3 trial (NCT04951622) is evaluating the treatment in adults, and the Phase 2/3 VIBRANCE-MG study (NCT05265273) is doing the same in children.

Vivacity-MG trial

The Phase 2 Vivacity-MG study enrolled 68 adults with gMG who had an inadequate response to standard-of-care therapy, most of whom (94.1%) were positive for autoantibodies targeting AChRs. Participants were randomly assigned to receive a placebo or one of four nipocalimab regimens — 5 mg/kg or 30 mg/kg once monthly, 60 mg/kg every two weeks, or a single dose of 60 mg/kg — for eight weeks (two months) on top of standard care.

The study’s main goals were to evaluate nipocalimab’s safety and effects on the scores of the MG Activities of Daily Living (MG-ADL) scale, a patient-reported measure of disease severity in which higher scores indicate more severe disease.

Results showed nipocalimab was well tolerated and led to a dose-dependent reduction in the levels of circulating IgGs that could be detected within the first week of treatment.

Dose-dependent reductions in MG-ADL scores were also observed relative to the placebo over the two-month treatment period, reflecting an easing of disease severity, although no individual dose was statistically significant from the placebo. Patients who experienced greater IgG reductions in the bloodstream tended to have greater MG-ADL score reductions.

Ongoing trials

The ongoing Phase 3 Vivacity-MG3 trial is testing nipocalimab’s safety and efficacy in 199 adults with gMG who had an insufficient response to standard therapy. Most patients (153 in total) were positive for MG-causing autoantibodies, including those targeting AChRs, muscle specific tyrosine kinase, and/or low density lipoprotein receptor-related protein 4.

Trial participants were randomly assigned to receive infusions of nipocalimab (15 mg/kg after an initial 30 mg/kg loading dose) or a placebo once every two weeks plus standard care for 24 weeks, or about six months. The study’s main goal was to evaluate changes in MG-ADL scores over the course of six months in autoantibody-positive patients.

Top-line results showed the study met its main goal of achieving a significant easing of disease severity with nipocalimab. Specifically, MG-ADL scores decreased by a mean of 4.7 points from the study’s start to the last three weeks of treatment in the nipocalimab group, a significant drop compared with the mean 3.25-point reduction observed in the placebo group.

Moreover, significantly more nipocalimab-treated patients achieved a clinically meaningful response, defined as a minimum 2-point improvement in MG-ADL scores relative to the placebo group in the last few weeks of treatment.

Similarly, the treatment led to significant reductions (improvements) in the scores of the Quantitative MG (QMG) scale, a clinician-rated measure of MG severity, where scores dropped by a mean of 4.86 points with nipocalimab and by 2.05 points with the placebo.

After completing the main trial, participants can opt to enter an open-label extension phase, where all will receive nipocalimab for up to two years. The study is expected to finish in 2026.

The Phase 2/3 VIBRANCE-MG study seeks to evaluate the effects of nipocalimab in 12 gMG patients, ages 2-17, who have responded inadequately to standard-of-care treatment. All of them will receive infusions of nipocalimab once every two weeks for about six months. After the main study, participants will be able to enter a long-term extension phase, where they’ll continue to receive nipocalimab for up to three years.

The study’s main goals are to evaluate changes in blood IgG levels, along with assessing nipocalimab’s safety and pharmacological properties. Changes in MG-ADL and QMG scores, as well as life quality assessments will also be evaluated as secondary outcome measures. VIBRANCE-MG is expected to finish in 2025.

Common side effects of nipocalimab

The most common side effects seen in gMG patients treated with nipocalimab in clinical trials include:

• diarrhea
• headache
• cold-like symptoms (nasopharyngitis)
• rash
• back pain
• dizziness
• high blood pressure
• musculoskeletal pain
• swelling

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