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The submission was based on results from the phase 3 Vivacity-MG3 study, which demonstrated nipocalimab’s superiority over placebo when added to standard of care in patients with generalized myasthenia gravis.
Bill Martin, PhD
(Credit: LinkedIn)
Johnson & Johnson has announced that it submitted a biologics license application (BLA) to the FDA seeking the initiation approval of nipocalimab for the treatment of patients living with generalized myasthenia gravis (gMG).1 Nipocalimab is designed to exclusively block binding of immunoglobulin G (IgG) to the neonatal fragment crystallizable (Fc) receptor (FcRn) resulting in decreased levels of circulating IgG, including IgG autoantibodies.
The application was supported by data from the phase 3 Vivacity-MG3 study (NCT04951622) which showed that nipocalimab plus standard of care (SOC) achieved superiority over placebo plus SOC as measured by the primary end point of improvement in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score from baseline over 24 weeks.2 In the trial, patients who received nipocalimab plus SOC improved by 4.70 points on the MG-ADL, which was significantly more than the 3.25-point improvement from baseline observed in the placebo plus SOC group over weeks 22, 23 and 24 (P = .002)
"We are encouraged by the potential of nipocalimab to provide sustained disease control for people living with generalized myasthenia gravis, a chronic, life-long disease," Bill Martin, PhD, global therapeutic area head, neuroscience, Johnson & Johnson Innovative Medicine, said in a statement.1 "The filing for approval of nipocalimab represents an important step forward as Johnson & Johnson continues to push the boundaries of research to develop innovative solutions to treat autoantibody-driven diseases, building on decades of expertise in neuroscience and immunology. We look forward to working with the FDA in their review of the data supporting the submission."
Vivacity-MG3 was a double-blind, placebo-controlled trial aimed to measure sustained efficacy and safety of nipocalimab over 24 weeks in 199 adult participants who were antibody positive or negative gMG and had insufficient response (MG-ADL at least 6) to ongoing SOC therapy. In the study, investigators randomized participants 1:1 to nipocalimab plus current SOC (30 mg/kg IV loading dose followed by 15 mg/kg every 2 weeks) or placebo plus current SOC. Baseline demographics were balanced across arms (nipocalimab, n = 77; placebo, n = 76). The primary end point of the study was the mean change in MG-ADLa score from baseline over weeks 22, 23 and 24 and a key secondary end point included change in Quantitative Myasthenia Gravis (QMG) score from baseline over 24 weeks.
“The sustained response of nipocalimab over 6 months among this broad myasthenia gravis population is an important finding given the chronic, unpredictable exacerbations typically seen with myasthenia gravis,” Carlo Antozzi, MD, neuroimmunology and muscle pathology unit of the Neurological Institute Foundation C. Besta in Milan, Italy, said in a statement.2 “We are encouraged by the potential of nipocalimab to uniquely help address this gap for people living with myasthenia gravis.”
Earlier this year, at the 2024 European Academy of Neurology (EAN) Congress, researchers reported that patients treated with nipocalimab plus SOC showed a significant improvement in QMG score compared with placebo plus SOC over weeks 22 and 24 (P <.001), in addition to enhancements in strength and function of different muscle groups. Additionally, MG-ADL response had a significant improvement in nipocalimab plus SOC compared with placebo plus SOC (P = .021) over weeks 22, 23 and 24. Above all, safety and tolerability results with nipocalimab were consistent with findings from previous studies. Furthermore, the overall incidence of adverse events, serious adverse events, and adverse events that led to discontinuation was similarly reported to that in the placebo plus current SOC group.
“We are thrilled to present yet another dataset for nipocalimab at the EAN 2024 Annual Meeting highlighting our commitment to providing innovative treatments for autoantibody-driven diseases,” Katie Abouzahr, MD, vice president, autoantibody and maternal fetal immunology disease area leader, Johnson & Johnson Innovative Medicine, said in a statement.2 “We are developing transformative therapies that have the potential to address significant unmet patient need.”
At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, investigators presented research on the key non-clinical properties and clinical outcomes of nipocalimab in gMG.3 Cell based assays, in vivo mouse and cynomolgus monkey studies, and human clinical data were used, with binding epitopes on FcRn determined through x-ray crystallography. All told, results showed that nipocalimab demonstrated a consistent dose-dependent pharmacokinetic-pharmacodynamic-receptor occupancy relationship in nonclinical and clinical studies leading to rapid decreases in IgG including IgG autoantibodies correlating to clinical response in gMG.
Nipocalimab remains investigational for gMG and is currently the only anti-FcRn currently being studied across the 3 segments of autoantibody diseases: maternal fetal, rare autoantibody, and prevalent rheumatology. Katie Abouzahr, MD, a study author on the research paper, sat down with NeurologyLive® following the meeting to discuss nipocalimab and the promise behind its mechanism of action. Abouzahr, vice president, Autoantibody Portfolio and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson, talked about some of its specific unique properties and how it differs from other MG agents. In the clip below, she discussed how the pH-independent properties of the therapy and its ability to not exert pharmacology in the fetus has allowed researchers to evaluate its potential in autoantibody driven diseases.
