Abstract Details

Title Assessing the Relationship Between Immunoglobulin G Level and Efficacy of Nipocalimab Measured Using Myasthenia Gravis-activities of Daily Living scale

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P4 - Poster Session 4 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-006

Objective To explore the longitudinal relationship between immunoglobulin G (IgG) level and Myasthenia Gravis-Activities of Daily Living (MG-ADL) score using semi-mechanistic pharmacometrics modeling with data from clinical studies of nipocalimab in generalized myasthenia gravis (gMG) and healthy volunteers.

Background In gMG, IgG-based autoantibodies attack the neuromuscular junction, causing muscle weakness. Nipocalimab, a neonatal fragment crystallizable receptor (FcRn) blocker, prevents IgG recycling and thus lowers levels of circulating IgG antibodies, including pathogenic autoantibodies, thereby improving symptoms of gMG.

Design/Methods Data from five phase-1, one phase-2, and one phase-3 (Vivacity-MG3) clinical studies were analyzed to characterize pharmacokinetics ([PK]; 3,429 serum nipocalimab concentrations [n=277]), pharmacodynamics ([PD]; 4,441 serum IgG concentrations [n=421] and 1,247 FcRn receptor occupancy data [n=78]). To establish the longitudinal relationship between IgG and MG-ADL, 2,317 absolute change from baseline (CFB) MG-ADL scores were analyzed in seropositive (anti-acetylcholine receptor, anti-muscle-specific receptor tyrosine kinase, anti-lipoprotein receptor-related protein-4) participants with gMG (n=220). A previously developed nonlinear mixed-effects model was used. The effects of baseline demographics and clinical characteristics on PK, PD, and MG-ADL parameters were investigated.

Results The previous model captured serum nipocalimab and total serum IgG concentrations of the Phase3 data well. MG-ADL CFB drug effect was linearly related to IgG %CFB at 0.28 points per 10% IgG %CFB. In the patient population, this resulted in approximately 2-points MG-ADL reduction for the nipocalimab-induced 70% IgG reduction. The slope of the regression line was dependent on baseline MG-ADL score. Age, body weight, race, ethnicity, sex, autoantibody status, gMG background therapy and gMG duration did not have a clinically relevant impact.

Conclusions The model confirmed IgG %CFB drives nipocalimab effect on MG-ADL. These results support that total serum IgG reduction is a good predictor for efficacy in gMG, allowing for comparison of clinical effect across FcRn inhibitors.

Authors/Disclosures
Zabeen K. Mahuwala, MD, FAAN (University of Kentucky, KY Clinic Neurology Department) PRESENTER	Dr. Mahuwala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Mahuwala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for academic CME. Dr. Mahuwala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen Scientific affairs. Dr. Mahuwala has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for amgen. The institution of Dr. Mahuwala has received research support from UCB, . The institution of Dr. Mahuwala has received research support from Alexion . The institution of Dr. Mahuwala has received research support from argenx . The institution of Dr. Mahuwala has received research support from immunovant.
Ruben Faelens, PhD	Mr. Faelens has received personal compensation for serving as an employee of J&J Innovative Medicine.
Belen Valenzuela, PhD	Dr. Valenzuela has nothing to disclose.
Martine Neyens, BSc	Mrs. Neyens has received personal compensation for serving as an employee of Johnson&Johnson.
Yaowei Zhu, PhD (Janssen Research & Development, LLC)	Dr. Zhu has received personal compensation for serving as an employee of Johnson & Johnson.
Jocelyn H. Leu, PhD, Pharm/PhD	Dr. Leu has received personal compensation for serving as an employee of Johnson and Johnson. Dr. Leu has stock in Johnson and Johnson.
Marie Fitzgibbon, PhD	Dr. Fitzgibbon has stock in Johnson & Johnson.
Sindhu Ramchandren	No disclosure on file
Juan-Jose Perez Ruixo (Johnson & Johnson, Beerse, Belgium)	No disclosure on file

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