ADAPT NXT: Fixed Cycles or Every‐Other‐Week IV Efgartigimod in Generalized Myasthenia Gravis DOI Creative Commons
Ali A. Habib, Kristl G. Claeys, Vera Bril

et al.

Annals of Clinical and Translational Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

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 4 once‐weekly infusions, with weeks between cycles) or cycle followed by every‐other‐week (Q2W) dosing. Methods Adult participants anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis (gMG) were 3:1 to Q2W (10 mg/kg intravenously) for 21 weeks. The primary endpoint was mean change from baseline total Myasthenia Gravis Activities Daily Living (MG‐ADL) score averaged across Results Sixty‐nine treated (fixed cycles, n = 17; Q2W, 52). Least squares (LS) (95% CI) MG‐ADL Weeks 1 −5.1 (−6.5 −3.8) arm −4.6 (−5.4 arm. Clinical improvements observed scores as early Week maintained throughout study. Achievement minimal symptom expression (MG‐ADL: 0–1) occurred 47.1% ( 8/17) 44.2% 23/52) arms, respectively. Efgartigimod well tolerated; COVID‐19, headache, upper respiratory tract infection most common treatment‐emergent adverse events. Interpretation results rapid, robust, sustained clinically meaningful improvement. These build upon previous studies provide additional approaches achieve sustain clinical efficacy patients gMG.

Language: Английский

The therapeutic age of the neonatal Fc receptor DOI Open Access
Michał Pyzik, Lisa K. Kozicky, Amit Gandhi

et al.

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(7), P. 415 - 432

Published: Feb. 1, 2023

Language: Английский

Citations

115
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis DOI Creative Commons
James F. Howard, Vera Bril, Tuan Vu

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 16, 2024

Objective ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG). Methods was an open-label, single-arm, multicenter, up to 3-year extension pivotal phase 3 ADAPT study. Efgartigimod administered treatment cycles 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation subsequent individualized based on clinical evaluation. Safety endpoints included incidence severity adverse events. Efficacy disease using Myasthenia Gravis-Activities Daily Living (MG-ADL) Quantitative Gravis (QMG) scores. Results As January 2022, 151 had rolled over 145 received ≥1 dose efgartigimod, whom, 111 (76.6%) were AChR-Ab+ 34 (23.4%) AChR-Ab−. Mean study duration (treatment plus follow-up) 548 days, 17 cycles, corresponding 217.6 participant-years exposure. In overall population, 123 (84.8%) reported treatment-emergent event; most frequent headache (36 [24.8%]), COVID-19 (22 [15.2%]), nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) mean MG-ADL QMG scores seen as early 1 week following first across multiple AChR-Ab− participants. Maximal improvements aligned onset magnitude total IgG AChR-Ab reductions. For at any time point each more than 90% a maximum reduction ≥2 points score; 7 which measured, 69.4% 91.3% demonstrated ≥3 score. Many well beyond CMI thresholds. year combined follow-up between ADAPT+, number annualized 4.7 (median [range] 5.0 [0.5–7.6]). Conclusion corroborate substantial support its efficacy, dosing regimen for gMG. Clinical trial registration https://classic.clinicaltrials.gov/ct2/show/NCT03770403 , NCT03770403.

Language: Английский

Citations

31
Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study DOI
Carlo Antozzi, Tuan Vu, Sindhu Ramchandren

et al.

The Lancet Neurology, Journal Year: 2025, Volume and Issue: 24(2), P. 105 - 116

Published: Jan. 22, 2025

Language: Английский

Citations

6
Effects of efgartigimod treatment on humoral and cellular immune responses: analysis of T-cell-dependent antibody response in cynomolgus monkeys DOI Creative Commons

Ornella Binazon,

Mario Cocco, Daniel Thwaites

et al.

Journal of Immunotoxicology, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 13, 2025

Efgartigimod is a human IgG1 antibody Fc fragment that reduces IgG levels through neonatal receptor blockade. This study evaluated whether efgartigimod affects the generation of T-cell-dependent antibodies and cellular immune responses to keyhole limpet hemocyanin (KLH) immunization in non-human primates. Cynomolgus monkeys received or vehicle control intravenously for 11 wk, followed by recovery phase. KLH challenges occurred during both dosing phase No statistically significant differences emerged anti-KLH IgM between groups. Likewise, comparable KLH-specific T cell were observed Anti-KLH titers lower efgartigimod-treated animals compared with controls only after first boost KLH, coinciding decreases total animals, returned baseline end Taken together, these results indicate does not suppress class-switching. The findings this are consistent efgartigimod's pharmacological mechanism action suggest impair effective responses.

Language: Английский

Citations

3
Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain DOI Creative Commons
Nathan T. Fiore,

Kendal F. Willcox,

Dorsa Dayani

et al.

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
Novel Immunotherapies for Myasthenia Gravis DOI Creative Commons
Sruthi Nair, Saiju Jacob

ImmunoTargets and Therapy, Journal Year: 2023, Volume and Issue: Volume 12, P. 25 - 45

Published: April 1, 2023

Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG long-term toxicities of the medications have been major concerns with conventional therapies. Advances in immunology pathogenesis ushered an era newer therapies which are more specific efficacious. Complement neonatal Fc receptor blockers target disease-specific pathogenic mechanisms linked to myasthenia proven their efficacy pivotal clinical studies. B cell-depleting agents, specifically rituximab, also emerged as useful treatment severe MG. Many biologicals pipeline diverse stages development. This review discusses evidence novel issues related use.

Language: Английский

Citations

40
Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis DOI Creative Commons
Carlo Antozzi, Jeffrey T. Guptill, Vera Bril

et al.

Neurology, Journal Year: 2023, Volume and Issue: 102(2)

Published: Dec. 21, 2023

Background and ObjectivesTo evaluate in a phase 2 study the safety efficacy of IV nipocalimab, fully human, antineonatal Fc receptor monoclonal antibody, patients with generalized myasthenia gravis (gMG).MethodsPatients gMG inadequate response to stable standard-of-care (SOC) therapy were randomized 1:1:1:1:1 receive either placebo every weeks (Q2W) or one 4 nipocalimab treatments: 5 mg/kg once (Q4W), 30 Q4W, 60 Q2W each for 8 weeks, single dose, addition their background SOC therapy. Infusions (placebo nipocalimab) all groups maintain blinding. The primary endpoint was incidence treatment-emergent adverse events (TEAEs), including serious special interest. change from baseline day 57 Myasthenia Gravis-Activities Daily Living (MG-ADL) total scores. Dose at analyzed linear trend test over placebo, groups.ResultsSixty-eight (nipocalimab: n = 54; 14) randomized; 64 (94.1%) positive antiacetylcholine autoantibodies, (6%) antimuscle-specific tyrosine kinase autoantibodies. Fifty-seven (83.8%) completed treatment through 57. combined group compared demonstrated similar incidences TEAEs (83.3% vs 78.6%, respectively) infections (33.3% 21.4%, respectively). No deaths discontinuations due no interest (grade ≥3 infection hypoalbuminemia) observed treatment. A statistically significant dose MG-ADL (p 0.031, trend).DiscussionNipocalimab generally safe, well-tolerated, showed evidence dose-dependent reduction scores this study. These results support further evaluation gMG.Trial Registration InformationClinical Trials Registration: NCT03772587; first submitted December 10, 2018; EudraCT Number: 2018-002247-28; November 30, date patient dosed April 2019.Classification EvidenceThis provides Class I that gMG, it did not significantly improve any individual but improved across doses.

Language: Английский

Citations

29
Subcutaneous efgartigimod PH20 in generalized myasthenia gravis: A phase 3 randomized noninferiority study (ADAPT-SC) and interim analyses of a long-term open-label extension study (ADAPT-SC+) DOI Creative Commons
James F. Howard, Tuan Vu, George Li

et al.

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(5), P. e00378 - e00378

Published: Sept. 1, 2024

Language: Английский

Citations

14
Batoclimab vs Placebo for Generalized Myasthenia Gravis DOI
Chong Yan,

Yao-Xian Yue,

Yuzhou Guan

et al.

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(4), P. 336 - 336

Published: March 4, 2024

Importance Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in circulation alleviate symptoms patients with generalized MG. Objective To examine efficacy safety profile of batoclimab, a monoclonal IgG1 antibody, Design, Setting, Participants This was multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers China. Adult 18 years or older MG were screened, those who antibody positive enrolled. Intervention Eligible received batoclimab matching placebo addition standard care. Each treatment cycle consisted 6 weekly subcutaneous injections 680 mg, followed 4 weeks observation. A second required continuing treatment. Main Outcome Measure primary outcome sustained improvement, as defined 3-point greater reduction Gravis Activities Daily Living (MG-ADL) score baseline for more consecutive first individuals acetylcholine muscle-specific kinase antibodies. Results total 178 adult 132 randomly assigned, 131 tested antibodies, 1 negative (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) rate MG-ADL improvement antibody-positive 31.3% (20 64) group vs 58.2% (39 67) (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). diverged between 2 groups early week 2. mean (SE) maximum difference occurred after last dose (day 43, 1.7 [0.3] 3.6 group; difference, −1.9; −2.8 −1.0; nominal < rates treatment-related severe treatment-emergent adverse events 36.9% (24 65) 7.7% (5 70.1% (47 3.0% (2 group, respectively. Conclusions Relevance Batoclimab increased well tolerated Clinical effects extent IgG similar previously reported rozanolixizumab. Future studies large sample size are needed further understand batoclimab. Trial Registration ClinicalTrials.gov Identifier: NCT05039190

Language: Английский

Citations

13
Differential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin DOI Creative Commons
Guanglong Ma, Andrew R. Crowley,

Liesbeth Heyndrickx

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(10)

Published: May 7, 2024

The homeostasis of IgG is maintained by the neonatal Fc receptor, FcRn. Consequently, antagonism FcRn to reduce endogenous levels an emerging strategy for treating antibody-mediated autoimmune disorders using either FcRn-specific antibodies or engineered fragment. For certain antibodies, this approach has resulted in reductions serum albumin, other major ligand transported Cellular and molecular analyses a panel antagonists have been carried out elucidate mechanisms leading their differential effects on albumin homeostasis. These identified 2 processes underlying decreases during blockade: increased degradation competition between antagonist binding. findings potential implications design drugs modulate function.

Language: Английский

Citations

9