Investigational Nipocalimab Demonstrates Efficacy and Safety in Adolescent Population of Myasthenia Gravis

Jonathan Strober, MD

New data from the phase 2/3 VIBRANCE-MG study (NCT05265273) showed that treatment with nipocalimab (Johnson & Johnson), an investigational agent under review, was safe and efficacious in treating adolescents with generalized myasthenia gravis (gMG). Adolescents with gMG, which make up about 10% of new cases, have traditionally not been included in drug trials, raising the significance of these findings.^1,2

Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, the study featured 7 adolescents aged 12-18 with seropositive gMG. Of these, 5 completed the 24-week treatment period. Led by Jonathan Strober, MD, director of Clinical Services for Child Neurology and director of the Muscular Dystrophy Clinic at UCSF Benioff Children’s Hospital, nipocalimab was administered as a 30 mg/kg intravenous (IV) loading dose followed by 15 mg/lg IV every 2 weeks.

The patient population, which were on stable therapy but inadequately controlled, had a mean age of 14.1 years (SD, 1.86). In the study, treatment with nipocalimab results in statistically significant reduction in total serum immunoglobulin (IgG), the primary end point, at week 24. Overall, the mean percent change from baseline to week 24 for total serum IgG was –68.98% (SD, 7.561).

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As for the reasons why IgG levels was chosen as the primary end point, Strober told NeurologyLive^® that with this smaller population, safety was the utmost concern. "We’re really willing down the number of patients who can get in this study. [What we’re looking at] is whether the drug is doing what is supposed to be doing in adolescents like it’s doing in adults," he said. "That’s where the IgG level is key. Of course, the secondary end point is, if we drop the IgG level, does that correlate with a benefit in function and outcome in these patients?"

Coming into the study, the mean scores on Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) were 4.29 (SD, 2.430) and 12.50 (SD, 3.708), respectively. After 24 weeks of treatment, the mean change in MG-ADL was –2.40 (SD, 0.418) and mean change in QMG was –3.80 (SD, 2.683). Notably, 4 of the 5 patients who completed the study achieved minimum symptom expression, defined as MG-ADL scores of 0-1.

"Interestingly, it wasn’t as big of a difference as we saw in the adult population,” Strober said regarding change in MG-ADL and QMG scores. “But again, I think the smaller numbers make that difficult. These kids tended to start at a better place than the adults did, probably because the adults may be living longer with the condition before they get to this kind of phase. Almost all the kids in the study had very low functional abnormalities at the end of the initial period that we evaluated them."

Encouragingly, nipocalimab was well-tolerated, with no serious adverse events and no discontinuations because of adverse events. According to Strober, the safety profile was not much different from what the investigators expected. The most frequent adverse event was nasopharyngitis, followed by COVID-19, which was not related to the study drug. Patients who experienced COVID-19 during the trial also showed no significant adverse events while on nipocalimab, which Strober noted as "promising."

Nipocalimab, an investigational medicine, is designed to exclusively block binding of IgG to the neonatal fragment crystallizable (Fc) receptor resulting in decreased levels of circulating IgG, including IgG autoantibodies. In August, Johnson & Johnson announced it had submitted a biologics license application for nipocalimab as a treatment for adults living with gMG. The application was supported by data from the phase 3 Vivacity-MG3 study (NCT04951622) which showed that nipocalimab plus standard of care achieved superiority over placebo plus SOC as measured by the primary end point of MG-ADL score over a 24-week treatment period.

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REFERENCES
1. Nipocalimab demonstrates sustained disease control in adolescents living with generalized myasthenia gravis in Phase 2/3 study. News release. Johnson & Johnson. October 15, 2024. Accessed October 24, 2024. https://www.jnj.com/media-center/press-releases/nipocalimab-demonstrates-sustained-disease-control-in-adolescents-living-with-generalized-myasthenia-gravis-in-phase-2-3-study
2. Strober J, Black S, Ramchandren S, et al. Safety and effectiveness of nipocalimab in adolescent participants in the open label phase 2/3 Vibrance-MG clinical study. Presented at: 2024 AANEM Annual Meeting; October 15-18; Savannah, GA.
3. Johnson & Johnson seeks first approval of nipocalimab to treat broadest population living with antibody positive generalized myasthenia gravis. News Release. Published August 29, 2024. Accessed October 24, 2024. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-first-approval-of-nipocalimab-to-treat-broadest-population-living-with-antibody-positive-generalized-myasthenia-gravis