Clinical Insights From Phase 3 VIVACITY-MG3 Study of Nipocalimab in Generalized Myasthenia Gravis

Tuan Vu, MD

Myasthenia gravis (MG) is an autoantibody disease in which autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signaling, and impair or prevent muscle contraction. Although generalized MG may be managed with standard-of-care therapies, there is still a need to develop new treatments for those who may not respond well enough to or tolerate those therapies.

One agent, nipocalimab (Johnson & Johnson), is a promising monoclonal antibody, purposefully designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobuin G antibodies, while preserving immune function without causing broad immunosuppression. In addition to being developed for gMG, it remains the only anti-FcRn currently being studied across the 3 segments of autoantibody diseases: maternal fetal, rare autoantibody, and prevalent rheumatology.

At the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, investigators presented topline data from the phase 3 VIVACITY-MG3 trial of nipocalimab in gMG. The study featured 199 enrolled patients, 153 of which were seropositive, who were randomly assigned 1:1 to either nipocalimab or placebo for a 24-week treatment period.

During the meeting, study investigator and neuromuscular expert Tuan Vu, MD, sat down to provide an overview of the data, and some notes around nipocalimab, Vu, a professor of neurology at the University of South Florida, gave thoughts on the makeup of the trial, who was included, and what nipocalimab adds to the gMG treatment landscape. Furthermore, he commented on the rapidly evolving field of neuromuscular and electrodiagnostic medicine, shown by the research presented at AANEM 2024.

NeurologyLive^®: What was the patient makeup of this study?

Tuan Vu, MD: The study was conducted in patients with generalized myasthenia gravis. The inclusion and exclusion criteria were pretty standard across the board, similar to other studies in terms of MGFA classes, the minimum required MG-ADL scores, and other characteristics. This was an international study, and of interest, Asians made up about 30% of the population. It was well-done and well-controlled.

What were the most notable takeaways from VIVACITY-MG3?

The endpoint was measured as the change in MG-ADL from baseline to the average of weeks 22 to 24. We saw that the benefit, or the drop in MG-ADL, was very rapid within the first week or so, and was maintained throughout the course of the study. The study met its primary endpoint, showing a statistically significant change in MG-ADL, and also a significant change in QMG, which was the secondary measure. The time of stability in responders was also met, but the early response rate did not meet statistical significance. So, some of the later points weren’t calculated, but overall, numerically, the values were in favor of the nipocalimab treatment group.

What did the safety profile look like?

It was very well tolerated. There were no new safety signals identified, which is really encouraging.

What does nipocalimab bring to the MG treatment landscape?

So, the two available drugs on the market right now are given cyclically in response to patients' symptoms. This study was a bit different in that it was given IV every two weeks after a loading dose at baseline. The study showed that the response was more steady across the board. We saw a 69% decrease in total IgG and roughly a 65% decrease in AChR antibody levels, which corresponded to the changes in both QMG and MG-ADL.

Were there any domains of the MG-ADL that nipocalimab was especially effective on?

The subdomain analysis is still ongoing, and I suspect that will be published in the future, but I don’t have that data right now.

How does the research and data being presented at AANEM speak to where we are in treating neuromuscular disorders?

Up until 2017, we didn’t have anything new in the treatment of MG for a long, long time. Since then, there have been five new drugs on the market. At this meeting, we’re now hearing about positive results for B cell-directed therapy, in addition to the positive results for nipocalimab, which is a more downstream approach. There’s a lot of new stuff going on, so the future for MG looks really exciting. There will be more options in the future. It’s never good to have a disease, but if you had to have something, MG seems to be one where we’ll have a lot of treatment options.

Transcript edited for clarity.