ADAPT NXT: Fixed Cycles or Every-Other-Week IV Efgartigimod in Generalized Myasthenia Gravis

Abstract

Objective: This phase 3b, open-label, randomized ADAPT NXT study investigated the efficacy, safety, and tolerability of efgartigimod administered in either a fixed cycles dosing regimen (3 cycles of 4 once-weekly infusions, with 4 weeks between cycles) or a cycle followed by every-other-week (Q2W) dosing.

Methods: Adult participants with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) were randomized 3:1 to Q2W or fixed cycles dosing of efgartigimod (10 mg/kg intravenously) for 21 weeks. The primary endpoint was the mean change from baseline in total Myasthenia Gravis Activities of Daily Living (MG-ADL) score averaged across 21 weeks.

Results: Sixty-nine participants were treated (fixed cycles, n = 17; Q2W, n = 52). Least squares (LS) mean (95% CI) of the change from baseline in MG-ADL total score from Weeks 1 to 21 was -5.1 (-6.5 to -3.8) in the fixed cycles arm and -4.6 (-5.4 to -3.8) in the Q2W arm. Clinical improvements were observed in MG-ADL total scores as early as Week 1 and were maintained throughout the study. Achievement of minimal symptom expression (MG-ADL: 0-1) from Weeks 1 to 21 occurred in 47.1% (n = 8/17) and 44.2% (n = 23/52) of participants in the fixed cycles and Q2W arms, respectively. Efgartigimod was well tolerated; COVID-19, headache, and upper respiratory tract infection were the most common treatment-emergent adverse events.

Interpretation: Efgartigimod administered as either fixed cycles or Q2W dosing results in rapid, robust, and sustained clinically meaningful improvement. These results build upon previous studies and provide additional efgartigimod dosing approaches to achieve and sustain clinical efficacy in patients with gMG.

Keywords: efgartigimod; generalized myasthenia gravis; myasthenia gravis activities of daily living; neonatal Fc receptor.

FIGURE 1

Study design. Green triangles indicate efgartigimod infusion. ^aIncluding NSISTs, corticosteroids, and/or AChEIs. If receiving corticosteroids and/or NSISTs, must be on a stable dose for ≥ 1 month prior to screening. ^bAll participants entering Part B will be transitioned to Q2W with the option to extend to Q3W dosing based on clinical judgment and guided by the MG‐ADL total score. AChEI, acetylcholinesterase inhibitor; AChR‐Ab+, acetylcholine receptor autoantibody positive; gMG, generalized myasthenia gravis; IgG, immunoglobulin G; IV, intravenous; MG‐ADL, Myasthenia Gravis Activities of Daily Living; MGFA, Myasthenia Gravis Foundation of America; NSIST, nonsteroidal immunosuppressive therapy; Q2W, every other week; Q3W, every third week.

FIGURE 2

Participant disposition. AE, adverse event; IV, intravenous; Q2W, every other week.

FIGURE 3

LS mean change from baseline in total MG‐ADL score across Weeks 1–21. Mixed model for repeated measurements analysis with treatment, visit, and treatment by visit interaction as fixed effects, and baseline total MG‐ADL score as a covariate. Solid data points indicate weeks in which efgartigimod was administered and open data points indicate weeks in which efgartigimod was not administered for each respective dosing regimen. CMI, clinically meaningful improvement; IV, intravenous; LS, least squares; MG‐ADL, Myasthenia Gravis Activities of Daily Living; Q2W, every other week.

FIGURE 4

Proportion of participants with increasing MG‐ADL threshold improvement during the study. CMI, clinically meaningful improvement; IV, intravenous; MG‐ADL, Myasthenia Gravis Activities of Daily Living; Q2W, every other week.