Phase 3b ADAPT NXT Study Confirms Efficacy of Cyclic and Biweekly Dosing of Efgartigimod in Generalized Myasthenia Gravis

New data from Part A of the phase 3b ADAPT NXT study (NCT04980495) showed that both cyclic and every-other-week dosing of intravenous efgartigimod (Vyvgart; Argenx), an FDA-approved treatment for patients with generalized myasthenia gravis (gMG), demonstrated significant improvement on the primary end point of change in MG Activities of Daily Living (MG-ADL). These findings build upon prior results from the phase 3 ADAPT/ADAPT+ trial (NCT03669588) and offer additional efgartigimod dosing approaches to maintain clinical efficacy in gMG.¹

In this study, 69 participants were treated with intravenous efgartigimod (cyclic, n = 17; every-other-week, n = 52). All told, researchers reported that the least squares mean of the change from baseline in MG-ADL total score from week 1 to week 21, the primary end point, was -5.1 (95% CI, -6.5 to -3.8) in the cyclic arm and -4.6 (95% CI, -5.4 to -3.8) in the every-other-week arm; changes remained similar through week 21. Notably, investigators observed clinically meaningful improvements in mean standard error MG-ADL total scores as early as week 1 (both arms; 95% CI, -2.0 [SE, 0.4]) and reported that they were maintained over time.

Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, the ADAPT NXT study assessed the efficacy, safety, and tolerability of efgartigimod administered either every-other-week or in fixed cycle dosing regimens among adult patients with anti-acetylcholine receptor antibody positive gMG. In the study, conducted by lead author Ali A. Habib, MD, an associate professor of neurology at UCI School of Medicine, and colleagues, participants were randomized 3:1 to every-other-week or cyclic (4 once-weekly infusions, 4 weeks between cycles) dosing of 10 mg/kg efgartigimod for a 21-week period. 

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Additional findings showed that achievement of minimal symptom expression (MG-ADL score 0-1) was reported in 47.1% of patients in the cyclic arm (n = 8) and 44.2% of participants in the every-other-week arm (n = 23). In terms of safety, authors noted that the treatment was well tolerated among the participants; the most common treatment-emergent adverse events included COVID-19, upper respiratory tract infection, and headache.

Presented at the 2022 AANEM Annual Meeting, held September 21-24, in Nashville, Tennessee, data from the ADAPT/ADAPT+ study of efgartigimod suggested that the treatment is similarly effective for patients who have anti-acetylcholine receptor antibody-seronegative (AChR-Ab–)gMG.² During one cycle of the ADAPT trial, 68.9% patients were treated with efgartigimod were deemed responders on the MG-ADL scale, defined as a 2 or more point improvement, compared with 63.2% of those on placebo. In addition, 52.6% of patients on active treatment were responders on the Quantitative Myasthenia Gravis (QMG) scale, considered a 3 or more point improvement, compared with 36.8% of those on placebo.

Conducted by coauthor James F. Howard, MD, distinguished professor of neuromuscular disease, and chief of the neuromuscular disorders section at University of North Carolina School of Medicine, and colleagues, these prior data revealed no clinically meaningful differences in safety or efficacy outcomes occurred between AchR-Ab+ and Ab– patients.

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REFERENCES
1. Habib AA, Claeys KG, Bril V, et al. Cyclic and Every-Other-Week Dosing of Intravenous Efgartigimod for Generalized Myasthenia Gravis: Part A of ADAPT NXT. Presented at: 2024 AANEM; October 15-18; Savannah, Georgia. Abstract 182.
2. Vu T, BrilV, Karam C, et al. Efficacy, Safety, and Tolerability of Efgartigimod in Anti-Acetylcholine Receptor Autoantibody Seronegative Patients with Generalized Myasthenia Gravtis: Integrated Interim Analysis of ADAPT/ADAPT+.Presented at: AANEM 2022; September 21-24; Nashville, TN. Abstract 105.