Nipocalimab Performs Well in Phase 3 Study of Myasthenia Gravis and Phase 2 Trial in Sjögren’s Disease

Katie Abouzahr, MD

Topline data from 2 pivotal studies assessing nipocalimab (Johnson & Johnson), an investigational agent in development for the treatment of autoantibody-driven diseases, have been released. All told, the agent met its primary end point in the phase 3 VIVACITY study (NCT04951622) of patients with generalized myasthenia gravis (gMG) and the phase 2 DAHLIAS (NCT04968912) dose-ranging study of adults with Sjögren’s disease (SjD).¹

VIVACITY was a multicenter study that consisted of a screening phase, a 24-week double-blind placebo-controlled phase, an open label extension lasting u to 2 years, and a follow-up safety visit up to 8 weeks after last infusion. Nipocalimab, a fully human, aglycosylated immunoglobulin G1 monoclonal antibody, met its primary end point, achieving statistically significant reduction in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score from baseline over weeks 22 to 24 compared with placebo.

Johnson & Johnson plan to present the full results from VIVACITY at an upcoming scientific medical congress, as well as engage with global regulatory authorities about bringing nipocalimab to patients with gMG. To date, nipocalimab is an investigational agent and is not approved. It has received orphan drug designation for several autoimmune disorders including warm autoimmune hemolytic anemia, hemolytic disease of the fetus and newborn, chronic inflammatory demyelinating polyneuropathy, and fetal and neonatal alloimmune thrombocytopenia.

"We look forward to sharing the comprehensive results of these important studies at upcoming scientific medical meetings," Katie Abouzahr, MD, vice president, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson, said in a statement.¹ "Johnson & Johnson is committed to addressing the immense unmet patient need in these chronic and debilitating autoantibody-driven diseases. We are the only company developing an anti-FcRn treatment in three key segments of autoantibody disease and have achieved proof of concept in each: Rare Autoantibody with gMG, Maternal Fetal Immunology with HDFN, and Prevalent Rheumatology with today's results in SjD building on our existing data in rheumatoid arthritis."

READ MORE: Exon-Skipping Drugs for Duchenne Shown to be Expensive, Rarely Used, With High Discontinuation Rates

DAHLIAS, a phase 2, double-blind, placebo-controlled, multicenter study, also met its primary end point, demonstrated by statistically significant reductions in clinESSDAI after 24 weeks of nipocalimab. According to the company, these data represented the first positive results of an investigational anti-FcRN treatment in patients with SjD, a disease for which there are no approved therapies available. In both DAHLIAS and VIVACITY, nipocalimab demonstrated a well-tolerated profile, further supporting its development.

The results of VIVACITY follow the previously conducted phase 2 VIVACITY-MG trial (NCT03772587). That study, published in Neurology in 2023, randomly assigned patients with gMG with inadequate response to stable standard-of-care therapy (SOC) 1:1:1:1 to either intravenous (IV) placebo every 2 weeks (Q2W), or one of 4 IV nipocalimab treatments: 5 mg/kg once every 4 weeks (Q4W), 30 mg/kg Q4W, 60 mg/kg Q2W each for 8 weeks, or a 60 mg/kg single dose, in addition to their background SOC therapy.²

Results from VIVACITY-MG showed that nipocalimab was generally safe, well-tolerated, with dose-dependent reductions in MG-ADL scores after 57 days of treatment. The study featured 68 patients (nipocalimab: n = 54; placebo: n = 14), of which 57 (83.8%) completed treatment through day 57. Overall, the combined nipocalimab group compared with the placebo group demonstrated similar incidences of treatment-emergent adverse events (83.3% vs 78.6%, respectively), and infections (33.3% vs 21.4%, respectively).

At the 2023 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, Janssen presented data on nipocalimab’s research program, which included patients with MG and other autoantibody diseases. Prior to the meeting, Hong Sun, MD, PhD, senior director, global compound development team leader, Janssen, sat down in an interview with NeurologyLive® to discuss a specific abstract in which findings highlighted the correlation between IgG and clinical efficacy in autoimmune diseases. In the clip below, she talked about the potential indications that nipocalimab covers in MG, how IgG serves as a clinical efficacy biomarker, and the implications it has for clinical trials in the future for MG treatment.

REFERENCES
1. Johnson & Johnson reports positive topline results for nipocalimab from a phase 3 pivotal study in generalized myasthenia gravis and a phase 2 study in Sjögren’s disease. News release. Johnson & Johnson. February 5, 2024. https://www.prnewswire.com/news-releases/johnson--johnson-reports-positive-topline-results-for-nipocalimab-from-a-phase-3-pivotal-study-in-generalized-myasthenia-gravis-gmg-and-a-phase-2-study-in-sjogrens-disease-sjd-302053304.html
2. Antozzi C, Guptill J, Bril V, et al. Safety and efficacy of nipocalimab in patients with generalized myasthenia gravis: results from the randomized phase 2 VIVACITY-MG study. Neurology. 2024;102(2):e207937