Nipocalimab bests placebo at easing gMG severity in Phase 3 trial
Vivacity-MG3 study enrolled nearly 200 people with gMG
Nipocalimab outperformed a placebo at easing the severity of generalized myasthenia gravis (gMG) in a Phase 3 clinical trial called Vivacity-MG3.
Full results from the trial were detailed in the study, “Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study,” published in The Lancet Neurology. The work was funded by nipocalimab’s developer Johnson & Johnson, which is now seeking nipocalimab’s approval in the U.S. and Europe.
“The Phase 3 Vivacity-MG3 data demonstrates our steadfast pursuit of researching and developing potential innovative and transformational approaches for autoantibody-driven diseases, such as gMG,” Sindhu Ramchandren, MD, executive medical director of neuroscience at Johnson & Johnson Innovative Medicine, said in a company press release. “We are delighted by the publication of this robust Phase 3 data in The Lancet Neurology as well as the Priority Review granted by the FDA. People living with gMG require additional effective immunoselective therapeutic options that can potentially preserve the ability to maintain a protective immune response even after reduction of [antibodies].”
MG is an autoimmune disease where the immune system creates self-reactive antibodies that target proteins involved in nerve-muscle communication, disrupting that process and leading to muscle weakness and fatigue.
Nipocalimab is an antibody-based therapy that blocks the activity of the neonatal Fc receptor, a protein that normally helps stabilize immunoglobulin G (IgG) antibodies circulating in the bloodstream and prevent their degradation. By blocking the protein, the therapy should accelerate the rate at which IgG antibodies are broken down, including those that drive MG.
Nipocalimab improves MG-ADL, lowers IgG antibodies
The Phase 3 Vivacity-MG3 trial (NCT04951622) enrolled nearly 200 people with gMG. About three-quarters of them were positive for the most common types of MG-driving antibodies, including those that target acetylcholine receptors (AChRs), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4). The participants were randomly assigned to either nipocalimab or a placebo, administered by an infusion directly into the bloodstream, every two weeks, for 24 weeks, or about six months. All the patients also received standard-of-care MG therapy.
The main goal was to evaluate the effect of treatment on the scores of the MG Activities of Living (MG-ADL), a standardized measure of disease severity that evaluates the impact of MG on daily activities and quality of life, from the study’s start to the last three weeks of treatment.
Consistent with previous top-line data, the results showed MG-ADL scores improved significantly more in those given nipocalimab than in those treated with a placebo (mean, 4.7 vs. 3.25 points).
Significantly more patients given nipocalimab saw their MG-ADL scores improve by at least 2 points (69% vs. 53%). Such a change “may be the difference between normal eating and frequent choking on food, or shortness of breath at rest and requiring the assistance of a ventilator.”
Nearly half (47%) of those on nipocalimab saw their MG-ADL scores improve by at least 50%, a level attained by 25% of those on placebo.
Subgroup analyses showed the differences in MG-ADL scores between nipocalimab and the placebo were statistically significant in patients positive for known MG-driving antibodies. There was no significant difference in antibody-negative patients, however. Johnson & Johnson is seeking nipocalimab’s approval for antibody-positive individuals.
“In the Vivacity-MG3 study, nipocalimab showed clinically meaningful and sustained efficacy over [six] months in a broad cohort of patients with antibody-positive (anti-AChR-positive, anti-MuSK-positive, or anti-LRP4-positive) generalised myasthenia gravis,” the researchers wrote.
Biomarker data also indicated nipocalimab led to strong reductions in IgG antibody levels within the first weeks after treatment started. Reductions in the levels of anti-AChR and anti-MuSK antibodies were also seen over six months.
Rates of adverse events — side effects and other safety-related issues — were similar among patients given nipocalimab or a placebo. Rates of serious adverse events were slightly lower among those on nipocalimab than those on a placebo (9% vs. 14%). There were three deaths in the nipocalimab group during the study, one due to a myasthenic crisis, which occurs when MG symptoms worsen and cause difficulty breathing, and two in the placebo group due to heart-related issues.
“Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over [six] months for a broad population of patients with generalized myasthenia gravis who are antibody-positive,” the researchers wrote.
Carlo Antozzi, MD, study co-author at the Neurological Institute Foundation C. Besta of Milan, Italy, said the results “further support the potential of nipocalimab to address the underlying cause of this debilitating autoantibody disease.”
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