FDA Grants Priority Review to FcRn Inhibitor Nipocalimab for Myasthenia Gravis

Author(s):

Key Takeaways

Nipocalimab targets FcRn to reduce IgG antibodies, showing efficacy in treating myasthenia gravis (MG) in the phase 3 Vivacity-MG3 trial.
The Vivacity-MG3 trial demonstrated significant improvements in MG-ADL and QMG scores for patients treated with nipocalimab plus standard-of-care.
Nipocalimab showed promise in adolescents with MG, achieving significant reductions in serum IgG and symptom expression in the VIBRANCE-MG study.
Safety and tolerability of nipocalimab were consistent with prior studies, with similar adverse event rates between treatment and placebo groups.

Nipocalimab’s biologics license application is supported by the phase 3 Vivacity-MG3 trial, in which the agent demonstrated superiority over placebo plus standard-of-care over a 24-week period.

Katie Abouzahr, MD

According to a recent announcement, the FDA has granted priority review to Johnson & Johnson’s investigational monoclonal antibody nipocalimab as a potential treatment for patients with myasthenia gravis (MG), an autoantibody disease. Nipocalimab, designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, remained currently under review by the European Medicines Agency.¹

If approved, nipocalimab will be available for antibody-positive patients with MG, including those with anti-acetylcholine (AChR), anti-muscle-specific kinase antibody (MuSK), and anti-low density lipoprotein-related protein 4 (LRP4) subtypes. The agent’s application is supported by the phase 3 Vivacity-MG3 study (NCT04951622), a large-scale trial that demonstrated nipocalimab’s superiority over placebo plus standard-of-care (SOC) therapy over a 24-week period.

"We welcome the FDA's decision to grant Priority Review for the treatment of generalized myasthenia gravis, which underscores the need for additional treatment options in a broad population of people living with gMG," Katie Abouzahr, MD, vice president, Autoantibody Portfolio and Maternal Fetal Immunology Disease Area Leader at Johnson & Johnson Innovative Medicine, said in a statement. "We are committed to working closely with the FDA to help bring nipocalimab as a potential treatment to certain patients living with gMG, and we especially thank the participants in the Phase 2 and 3 studies."

In Vivacity-MG3, 153 antibody-positive patients who’ve had insufficient response to ongoing SOC were randomly assigned 1:1 to nipocalimab plus SOC or placebo plus current SOC for a 24-week period. All told, those who received the investigational agent plus SOC improved by 4.70 points on Myasthenia Gravis Activities of Daily Living (MG-ADL), the primary end point, compared with improvements of 3.25-points in the placebo plus SOC group over weeks 22, 23, and 24 (P = .002).²

Patients treated with nipocalimab plus SOC also demonstrated significant improvements in Quantitative Myasthenia Gravis (QMG), a secondary outcome, in comparison with those in the placebo group (P <.001). In addition, nipocalimab plus SOC significantly improved MG-ADL response compared with placebo (P = .021) over weeks 22-24, with safety and tolerability consistent with prior studies. Between the 2 observed groups, investigators recorded a similar incidence of adverse events (AEs), serious AEs, and AEs that led to discontinuation.

Nipocalimab has also demonstrated promise in treating adolescents with GM, which make up about 10% of new cases and have traditionally not been included in drug trials. Otherwise known as the VIBRANCE-MG study (NCT05265273), the trial included 7 adolescents aged 12-18 with seropositive gMG who received nipocalimab as a 30 mg/kg intravenous loading dose followed by a 15 mg/lg IV every 2 weeks.³

Among those included, 5 completed the 24-week treatment period. Overall, patients in the study on nipocalimab showed statistically significant reductions in total serum IgG, the primary end point, after 24 weeks. Overall, the mean percent change from baseline was –68.98% (SD, 7.561). After 24 weeks, the mean MG-ADL change was –2.40 and QMG change was –3.80, with 4 of 5 patients achieving minimum symptom expression (MG-ADL scores of 0-1).

In late 2024, NeurologyLive launched a Peer Exchange panel discussion highlighting treatment advances in targeting underlying pathophysiology of MG. One of the episodes focused on nipocalimab, FcRn inhibitors, and the phase 3 trials that support them. In the clip below, the panelists discuss trial data for nipocalimab and batoclimab, and their potential impact on treatment approaches.

REFERENCES
1. Nipocalimab granted U.S. FDA Priority Review for the treatment of generalized myasthenia gravis. News release. Johnson & Johnson. January 9, 2025. Accessed January 15, 2025. https://www.prnewswire.com/news-releases/nipocalimab-granted-us-fda-priority-review-for-the-treatment-of-generalized-myasthenia-gravis-302346976.html
2. Nipocalimab pivotal Phase 3 trial demonstrates longest sustained disease control in FcRn class. News Release. Published June 28, 2024. Accessed January 15, 2025. https://www.jnj.com/media-center/press-releases/nipocalimab-pivotal-phase-3-trial-demonstrates-longest-sustained-disease-control-in-fcrn-class
3. 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.