Vivacity-MG3 Trial Confirms Nipocalimab’s Efficacy, Safety in Treating Generalized Myasthenia Gravis
Phase III Vivacity-MG3 trial shows that nipocalimab, an investigational FcRn blocker, significantly the improves symptoms of generalized myasthenia gravis with a manageable safety profile.
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Data from the Phase III Vivacity-MG3 trial (NCT04951622) show the investigational therapy nipocalimab improved the symptoms of generalized myasthenia gravis (gMG) with a manageable safety profile.1,2 The authors of the study, published in The Lancet Neurology, stated these results further reinforce the potential of nipocalimab in the treatment of gMG, a rare, chronic autoimmune disease.3
“Nipocalimab has been shown in multiple clinical studies to help reduce IgG, including autoantibodies, among this broad population of antibody-positive adults with gMG. The positive results from the Vivacity-MG3 study further support the potential of nipocalimab to address the underlying cause of this debilitating autoantibody disease,” Carlo Antozzi, MD, Neuroimmunology and Muscle Pathology Unit of the Neurological Institute Foundation C. Besta of Milan, Italy, said in a press release. “It’s promising to see this positive data published in The Lancet Neurology as there is a continued need for additional approved targeted therapies with demonstrated safety profiles that offer sustained disease control for a broad range of antibody positive patients living with gMG.”1
Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody and acts as an anti-neonatal Fc receptor (FcRn). Earlier this month, the FDA granted Priority Review to a Biologics License Application for nipocalimab in the treatment of antibody-positive patients with gMG based on results of the Vivacity-MG3 trial.4
“Given burdensome side effects and long latency for efficacy with conventional agents, there is a continued need for [gMG] treatments that are safe and provide consistently sustained, long-term disease control,” the study authors wrote in The Lancet Neurology. “Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with [gMG] in a phase 2 study.”3
Trial Design
The randomized, double-blind, placebo-controlled, Vivacity-MG3 trial was conducted at 81 outpatient sites across 17 countries in Asia–Pacific, Europe, and North America that have experience with myasthenia gravis. Investigators enrolled adults older than 18 years of age with gMG that is inadequately controlled by standard-of-care therapy.
The trial enrolled 199 patients, of whom 153 were antibody positive, who were randomly assigned in a 1:1 ratio to receive nipocalimab at a 30 mg/kg loading dose followed by 15 mg/kg every two weeks for maintenance dosing or to receive placebo infusions every two weeks. Both cohorts also were administered standard-of-care therapy for 24 weeks. Randomization was based on antibody status, day one MG-ADL total score, and region.
The trial’s primary endpoint was difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL average total score across weeks 22-24 among the intention-to-treat cohort of patients who were antibody-positive. The trial also assessed adverse events (AEs) in those administered at least one dose of nipocalimab.
Trial Results
Between July 15, 2021, and Nov 17, 2023, among 98 patients administered nipocalimab and 98 administered placebo, the least-squares mean change in MG-ADL score from baseline to weeks 22-24 was –4·70 (SE 0·329) in the nipocalimab cohort compared to –3·25 (0·335) in the placebo cohort (difference –1·45 [95% CI –2·38 to –0·52]; p=0·0024). Reports of AEs occurred in 84% of patients in both cohorts, which included infections in 43% of patients in both cohorts and headache at 14% in the nipocalimab cohort and 17% in the placebo cohort. Serious AEs were reported in 9% of patients in the nipocalimab cohort compared to 14% in the placebo cohort. Three deaths were reported, with one patient in the nipocalimab cohort dying from myasthenic crisis and two patients dying in the placebo cohort from cardiac arrest and myocardial infarction, respectively.
The study authors concluded that nipocalimab added to standard-of-care therapies produced safe and sustained disease control over six months in a broad population of antibody-positive positive patients with gMG.
“The Phase III Vivacity-MG3 data demonstrates our steadfast pursuit of researching and developing potential innovative and transformational approaches for autoantibody-driven diseases, such as gMG,” Sindhu Ramchandren, MD, executive medical director, Neuroscience, Johnson & Johnson Innovative Medicine, said in the release. “We are delighted by the publication of this robust Phase 3 data in The Lancet Neurology as well as the Priority Review granted by the FDA. People living with gMG require additional effective immunoselective therapeutic options that can potentially preserve the ability to maintain a protective immune response even after reduction of IgG.”1
References
1. Findings from pivotal nipocalimab Phase 3 study in a broad antibody positive population of people living with generalized myasthenia gravis (gMG) published in The Lancet Neurology. News release. Johnson & Johnson. January 23, 2025. Accessed January 23, 2025. https://www.jnj.com/media-center/press-releases/findings-from-pivotal-nipocalimab-phase-3-study-in-a-broad-antibody-positive-population-of-people-living-with-generalized-myasthenia-gravis-gmg-published-in-the-lancet-neurology
2. A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis. ClinicalTrials.gov. Updated January 13, 2025. Accessed January 23, 2025. https://www.clinicaltrials.gov/study/NCT04951622
3. Antozzi, Carlo et al. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. The Lancet Neurology, Volume 24, Issue 2, 105 – 116.
4. Nipocalimab granted U.S. FDA Priority Review for the treatment of generalized myasthenia gravis. J&J. January 9, 2025. Accessed January 23, 2025. https://www.jnj.com/media-center/press-releases/nipocalimab-granted-u-s-fda-priority-review-for-the-treatment-of-generalized-myasthenia-gravis-gmg
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