Nipocalimab (M281)

Nipocalimab (M281) is an experimental therapy being developed to potentially ease the severity of myasthenia gravis (MG) and several other autoimmune diseases.

It originally was developed by Momenta Pharmaceuticals, which was acquired by Johnson & Johnson in 2020.

The infusion therapy is now being developed by Janssen, a subsidiary of Johnson & Johnson, and currently is being tested in clinical trials.

How does nipocalimab work?

MG is caused by the body’s immune system wrongly launching an attack against the neuromuscular junction — the place where nerve cells communicate with muscle cells. This attack is largely driven by self-reactive antibodies, also known as autoantibodies, and more specifically, by immunoglobulin G (IgG) autoantibodies.

The neonatal Fc receptor, or FcRn, is a protein that normally helps to prevent IgG antibodies circulating in the bloodstream from being degraded. Nipocalimab is a therapeutic antibody that is designed to block the activity of FcRn. In so doing, the therapy aims to increase the rate at which IgG autoantibodies are degraded, thereby reducing their levels in the bloodstream and easing MG severity.

Nipocalimab in clinical trials

Momenta sponsored a Phase 2 clinical trial, called Vivacity-MG (NCT03772587), which enrolled 68 adults with moderate-to-severe MG at more than 60 locations across North America and Europe. Some participants were randomly assigned to receive a placebo, while others were given one of four dosing regimens of nipocalimab: 5 or 30 mg/kg every four weeks, 60 mg/kg every two weeks, or 60 mg/kg as a single dose.

Participants in all five groups received a total of five intravenous (into-the-vein) infusions of either nipocalimab or a placebo every other week during the treatment period. Those in groups whose treatment did not follow the two-week dosing schedule received placebo infusions in between the doses in order to maintain the secrecy of the assigned treatment regimen.

The main goal of Vivacity-MG was to assess the effects of treatment on the MG Activities of Daily Living (MG-ADL) score, a validated measure of MG severity.

The trial results showed that 51.9% of participants given nipocalimab — across all doses — had a significant and durable reduction in MG-ADL scores for at least four consecutive weeks, or about one month. By comparison, only 15.4% of participants given a placebo experienced such a reduction in MG-ADL scores. Improvements tended to be rapid, occurring within two weeks of the treatment’s start.

The data also demonstrated that treatment with nipocalimab reduced IgG levels in the body. The highest dosage of the experimental therapy led to a sustained 80% drop in IgG levels. Notably, IgG reductions were found to be significantly associated with changes in the MG-ADL score. In other words, individuals attaining a greater reduction in IgG levels also tended to experience a more substantial lessening of symptoms.

Nipocalimab was generally well-tolerated in Vivacity-MG. There were no adverse events leading to treatment discontinuation, no dose-dependent increase in adverse event rates, and no serious adverse events deemed related to the investigational medication.

Janssen is currently conducting a Phase 3 clinical trial (NCT04951622) to further evaluate the safety and efficacy of nipocalimab in about 180 adults with MG at multiple locations around the globe. Participants will be given intravenous infusions of nipocalimab or a placebo every other week. The study’s main goal is to assess changes in MG-ADL scores after 24 weeks (about six months) of treatment. The biological effects of the therapy and its safety also will be assessed, as will the medicine’s impact on the participants’ quality of life

Other details

In addition to MG, nipocalimab is being investigated as a potential treatment for other conditions driven by IgG antibodies. The U.S. Food and Drug Administration has given nipocalimab both fast track and rare pediatric disease designations as a potential treatment for hemolytic disease of the fetus and newborn (HDFN), a condition in which antibodies from a pregnant woman’s body damage red blood cells of the developing baby.


Last updated: September 9, 2021


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