Symptoms of gMG controlled with long-term nipocalimab treatment
Johnson & Johnson seeks therapy's OK for antibody-positive gMG in US, Europe
Long-term treatment with nipocalimab led to sustained reductions in symptom severity among antibody-positive patients with generalized myasthenia gravis (gMG) in a Phase 3 clinical trial.
That’s according to new data presented by its developer, Johnson & Johnson, at the American Academy of Neurology (AAN) Annual Meeting this month in San Diego.
“These positive data underscore our commitment to helping develop potential innovative therapeutic options for patients living with autoantibody diseases, including gMG,” Katie Abouzahr, MD, vice president of autoantibody portfolio and maternal fetal immunology disease area leader at Johnson & Johnson Innovative Medicine, said in a company press release.
MG is an autoimmune disease where self-reactive antibodies disrupt the communication between nerve and muscle cells, leading to muscle weakness and fatigue.
Nipocalimab is designed to reduce MG-driving antibodies by blocking the activity of neonatal Fc receptor, a protein that normally helps prevent antibodies circulating in the blood from being destroyed.
“People living with generalized MG around the world endure daily challenges, such as difficulties swallowing, impaired speech, and muscle weakness. They deserve additional, effective treatment options that help address these challenges and provide sustained disease control and stability over time,” Abouzahr said.
Gains with nipocalimab treatment
Nipocalimab is being tested in a Phase 3 clinical trial called Vivacity-MG3 (NCT04951622), which enrolled nearly 200 people with gMG, most of whom were positive for 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 Vivacity-MG3 participants were randomly assigned to either nipocalimab or a placebo, in addition to standard of care.
The study’s main goal was to see if nipocalimab was better than a placebo at improving the scores of the MG Activities of Living (MG-ADL), a scale of disease severity that evaluates the impact MG has on day-to-day activities. After six months, the scores improved significantly more for antibody-positive patients given nipocalimab relative to a placebo, though there weren’t any differences among antibody-negative patients.
Johnson & Johnson is seeking nipocalimab’s approval for antibody-positive gMG in the U.S. and Europe, based on these findings.
Another measure of MG severity called the Quantitative MG (QMG) was also tracked in Vivacity-MG3. Results from this score were detailed in a presentation titled, “Efficacy of Nipocalimab, a Novel Neonatal Fragment Crystallizable Receptor Blocker, as Measured Using Quantitative Myasthenia Gravis Assessment: Findings from the Phase 3 Placebo-controlled Vivacity-MG3 Study.”
QMG scores improved by a mean of 4.9 points after six months for those given nipocalimab, but by only 2 points with a placebo. A difference between the nipocalimab and placebo arms was evident within two weeks of starting treatment.
Within eight weeks of starting treatment, more than 70% of those on nipocalimab saw a gain of at least 3 points in QMG scores. Among those on a placebo, less than half had such an improvement within that time. Those given nipocalimab were about four times more likely to see their QMG scores improve by at least 3 points and sustain that improvement at least 20 weeks.
“These results indicate that nipocalimab … demonstrated disease control in patients with gMG, as evidenced by significant improvements in QMG scores,” the researchers wrote.
Results of open-label extension study
After the placebo-controlled part of Vivacity-MG3 ended, the participants could join an open-label extension study where all are being treated with nipocalimab and monitored for long-term outcomes. Findings from this study were shared in a poster titled, “Long-term Safety and Efficacy of Nipocalimab in Generalized Myasthenia Gravis: Vivacity-MG3 Open-label Extension Phase Results.”
A total of 137 antibody-positive patients entered the extension. After 60 weeks, MG-ADL scores substantially improved relative to those seen before the study’s start — by a mean of 5.64 points for those given nipocalimab in the placebo-controlled part of the study and by 6.01 points for those given a placebo. For context, at the end of the six-month, placebo-controlled part of the study, MG-ADL scores improved by a mean of 4.7 points with nipocalimab and by 3.25 points with a placebo.
Long-term data also indicated nearly half of the antibody-positive patients who’d been on steroids when they entered the extension study were able to substantially reduce their steroid dose or stop taking them altogether. Safety data from the extension study and the original Phase 3 trial have been consistent.
“The sustained disease control seen over 84 weeks for nipocalimab is a key result given the chronic course of generalized MG and the significant burden on people living with this condition,” said Constantine Farmakidis, MD, associate professor of neurology at the University of Kansas Medical Center. “Overall, I am encouraged by these results that show improvement in disease control as measured by the MG-ADL and QMG scores across a broad population seropositive for AChR, MuSK, or LRP4 autoantibodies.”
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