Fixed-cycle and Continuous Dosing of Intravenous Efgartigimod for Generalized Myasthenia Gravis: Study Design of ADAPT NXT
Vera Bril1, Yessar Hussain2, Kelly Gwathmey3, Gregory Sahagian4, Ali Habib5, Kristl Claeys6, Elena Cortes-Vicente7, Edward Brauer8, Deborah Gelinas8, Anne Sumbul8, Rosa Jimenez8, Daniela Hristova8, Renato Mantegazza9
1Ellen & Martin Prosserman Centre for Neuromuscular Diseases, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada, 2Austin Neuromuscular Center, Austin, Texas, 3Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, 4The Neurology Center of Southern California, Carlsbad, California, 5Department of Neurology, University of California, Irvine, Irvine, California, 6Department of Neurology, University Hospitals Leuven, Leuven, Belgium, 7Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 8argenx, Ghent, Belgium, 9Department of Neuroimmunology and Neuromuscular Diseases, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy
Objective:

To evaluate the efficacy, safety, and tolerability of 10 mg/kg intravenous efgartigimod administered in a  fixed-cycle regimen (4 once-weekly infusions with a 4-week intertreatment period) or continuous dosing regimen (every 2 weeks).

Background:

Individualized cyclic administration of efgartigimod, a human immunoglobulin G1 Fc-fragment that blocks the neonatal Fc receptor, was well tolerated and efficacious in the ADAPT/ADAPT+ phase 3 trials of patients with generalized myasthenia gravis (gMG). The phase 3b ADAPT NXT study (NCT04980495) is investigating the efficacy and safety of efgartigimod in both continuous and fixed-cycle regimens.

Design/Methods:

Adult participants with acetylcholine receptor antibody positive gMG who had a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of ≥5 (with >50% of the score due to nonocular symptoms), and on a stable dose of ≥1 concomitant gMG treatment were recruited. After a 3-week induction period during which all randomized participants received a total of 4 efgartigimod infusions, 69 participants were randomized 3:1 to either continuous or fixed-cyclic dosing regimens for the initial 21-week comparison period. Thereafter, participants in the fixed-cycle arm received a final cycle before being rolled over to continuous every 2 week dosing while participants in the continuous dosing arm maintained every 2 week dosing. Participants were followed for an additional 105 week extension period, and participants who maintained clinical improvement had the option to reduce dosing frequency to every 3 weeks.


Results:

The primary endpoint is mean of the average change in MG-ADL total score from study baseline to Week 21 for each regimen. Safety, tolerability, and pharmacokinetic/pharmacodynamic effects are also being assessed. Results will be presented at AAN 2024.

Conclusions:

ADAPT NXT will provide important data on different treatment regimens, which will allow for further individualization of treatment with efgartigimod.

10.1212/WNL.0000000000206537