SAN FRANCISCO — Nipocalimab (Imaavy), a neonatal Fc receptor (FcRn) blocker that recently received FDA approval for generalized myasthenia gravis (gMG) in adolescents and adults, demonstrated long-term benefits in two open-label extension studies, researchers reported. 

In the initial Vibrance-MG phase 2/3 study, seven adolescents aged 12-18 years with gMG showed more than a 70% reduction in median total serum immunoglobulin G (IgG) levels by week 24, the end of the active treatment phase. 

The reductions in IgG levels were similar — reduced by a median of 60.6% — in three patients who reached week 72 in the open-label extension, reported Jonathan Strober, MD, pediatric neurologist, Benioff Children’s Hospitals, University of California, San Francisco. 

The Vivacity-MG3 open-label extension of a phase 3 trial in adults showed sustained disease control over 84 weeks, with 45% of patients able to reduce or discontinue corticosteroids, reported neurologist Tuan Vu, MD, of the University of South Florida, Tampa, Florida. 

“Once the placebo-treated patients transitioned to nipocalimab, they improved rapidly, matching the response seen by patients who had previously achieved it with nipocalimab,” Vu said about the adult study.

As for the adolescent study, Strober said, “There was a clinically meaningful reduction in the MG-ADL [Myasthenia Gravis Activities of Daily Living] score observed by week 4, and that was also maintained through both the active treatment and the long-term extension.”

The findings were presented here on October 29 at the American Association of Neuromuscular Electrodiagnostic Medicine (AANEM) 2025.

Adult Trial Data

Nipocalimab is a monoclonal antibody that blocks the FcRn, a process that can reduce circulating IgG antibodies. By blocking FcRn, “your IgG can’t be recycled, and your IgG levels drop,” Strober explained.

In April 2025, the FDA approved nipocalimab for the treatment of gMG in adults and adolescents aged 12 years or older.

The initial Vivacity-MG3 study in adults randomly assigned patients 1:1 to receive intravenous nipocalimab (30 mg/kg loading dose, then 15 mg/kg every 2 weeks for maintenance dosing) plus standard of care, or placebo plus standard of care for 24 weeks. 

The 87 patients in the nipocalimab arm who finished the trial reached the primary efficacy endpoint with a statistically significant improvement of 4.70 points on the MG-ADL score from baseline vs a 3.25-point improvement in the 82 patients in the placebo group (P = .002).

For the open-label extension trial, 66 of 76 patients who took a placebo were switched to nipocalimab (average age, 51.6 years; 57.6% female; 62.1% White; 1.5% Black; 4.5% not reported). In addition, 71 of 77 participants continued on nipocalimab (average age, 51.1; 64.8% female; 63.4% White; 31.0% Asian; 1.4% Black; 1.4% American Indian/Native Alaskan; 2.8% not reported).

Later, eight patients in the initial placebo group dropped out (7.6% due to adverse effects, 3.0% due to lack of efficacy, and 1.5% due to physician decision), and 15 dropped out of the initial nipocalimab group (5.6% due to adverse effects, 1.4% due to death unrelated to treatment, 7.0% due to withdrawal by patient, and 7.0% due to lack of efficacy).

The MG-ADL data demonstrated consistent benefit across both phases of the study in both the initial nipocalimab group and the initial placebo group. “At the end of 60 weeks of the open-label, both groups achieved between 5 and 6 points of improvement from baseline,” Vu reported.

He added that “as the mechanism of the drug is to reduce IgG level, we see a steady, very rapid reduction in IgG level that was maintained throughout the randomized control period and the open-label [period].”

No New Safety Issues

Regarding cardiovascular safety, Vu said, “The mean total cholesterol to HDL [high-density lipoprotein] ratio remained less than 4 and comparable to the placebo group throughout 84 weeks, and at this level, we don’t expect cardiovascular complications.”

As for adverse effects, “there were no new safety concerns despite continuous IgG lowering, and event rates were comparable to the double-blind placebo-controlled period in all nipocalimab-treated patients,” he said.

The initial Vibrance-MG3 study assigned participants aged 12 to < 18 years to an initial loading dose of intravenous nipocalimab 30 mg/kg followed by 15 mg/kg every 2 weeks. 

There were eight participants with gMG, Myasthenia Gravis Foundation of America class II-IV, with suboptimal response to current therapy (average age, 13.5 years; 87.5% female; 62.5% Asian; 25.0% unknown; 12.5% Black; 75.0% not Hispanic/Latino; 12.5% Hispanic/Latino; 12.5% unknown). The median MG-ADL total score was 3.5.

One of the eight participants was added following the earlier release of trial data, and the active-treatment trial is ongoing. During the long-term extension, investigators had the discretion to adjust doses to either 15 mg/kg every 2 weeks or 30 mg/kg every 4 weeks. Six patients entered the long-term phase. Of the six participants, one discontinued, five are ongoing, and three completed week 72.

At 72 weeks, median serum IgG was 3.3 g/L (range, 2.8-4.3) compared with 10.7 g/L (8.9-13.1) at baseline and 3.2 g/L (2.3-3.5) at week 24.

Two of three patients who reached week 72 continued to have symptom improvement via the MG-ADL score, Strober reported, although specific scores were not provided. The baseline score for subjects was 3.5 (range, 3.0-5.0), which was reduced to 1.0 (0.0- 3.0) at 24 weeks. 

At an average of 24.3 weeks of follow-up in the initial trial, 100% of eight patients had at least one treatment-emergent adverse effect (TEAE), but none were serious or led to discontinuation. Nasopharyngitis was most common (37.5%), followed by COVID (25.0%).

In the long-term phase, over an average of 44.3 weeks of follow-up, 66.6% of six patients had at least one TEAE. Nasopharyngitis was the most common (33.3%), followed by upper respiratory tract infection, migraine, diarrhea, and muscle spasms (16.7%). One patient had a serious adverse effect — gMG worsening — at week 84. Another subject had a case of influenza that temporarily stopped treatment.

A Novel Therapeutic

Emmanuelle Tiongson, MD, pediatric neurologist of Children’s Hospital Los Angeles and Keck School of Medicine of the University of Southern California, Los Angeles, who’s familiar with the adolescent study findings, told Medscape Medical News that nipocalimab “has a place in the novel therapeutics space in juvenile MG [myasthenia gravis].”

“I am using it currently as a second-line drug in patients 12 years or older or refractory patients, but the paradigm is shifting,” she said. “It may eventually become a first-line treatment.”

In regard to the findings, she said, “The extended data is telling us that this is a good maintenance medication, as the reduction of IgG and patient-reported scores stay stable. It is great that even with a rapid IgG reduction, the adverse events were minor, and there were no serious infections.”

“I am so glad that the scientific community is focusing on pediatric MG, as options have been very limited in the past in terms of on-label or FDA-approved treatment. We won’t have to fight with insurance companies to get pediatric patients the latest effective medications that the adults already have had access to,” she added.

Johnson & Johnson funded both studies. Strober disclosed having relationships with Scholar Rock, Argenx, Johnson & Johnson, Biogen, PTC, FibroGen, Biohaven, Pfizer, Pediatric Neurology, various law firms, and a research support source that is anonymous.

Vu disclosed having relationships with Alexion/AstraZeneca Rare Disease, Amgen, Argenx, Cartesians, Dianthus, Johnson & Johnson, Immunovant, Regeneron, RemeGen, UCB, Alexion, CSL Behring, ImmunAbs, and Dianthus. Several authors of both studies were employees of Johnson & Johnson. Other authors reported having various and multiple disclosures. Tiongson reported having no disclosures.