Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study
- PMID: 38810600
- DOI: 10.1016/j.pediatrneurol.2024.04.020
Eculizumab in Adolescent Patients With Refractory Generalized Myasthenia Gravis: A Phase 3, Open-Label, Multicenter Study
Abstract
Background: This study evaluated the efficacy and safety of eculizumab, a terminal complement C5 inhibitor, in juvenile generalized myasthenia gravis (gMG).
Methods: Adolescents aged 12 to 17 years with refractory anti-acetylcholine receptor (AChR) antibody-positive gMG received eculizumab (weekly induction [one to two doses of 600 mg or four doses of 900 mg] followed by maintenance doses [300 to 1200 mg] every two weeks for up to 26 weeks) in a phase 3, open-label multicenter study (NCT03759366). Change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score (primary end point) and secondary end points including Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score, Myasthenia Gravis Composite score, Myasthenia Gravis Foundation of America postintervention status, EuroQol 5-Dimensions (Youth) and Neurological Quality-of-Life Pediatric Fatigue questionnaire scores, as well as pharmacokinetics, pharmacodynamics, and safety, were recorded.
Results: Eleven adolescents (mean ± S.D. age 14.8 ± 1.8 years) were enrolled; 10 completed the primary evaluation period. Least-squares mean changes from baseline at week 26 were -5.8 (standard error [SE] 1.2; P = 0.0004) for QMG total score and -2.3 (SE 0.6; P = 0.0017) for MG-ADL total score. Overall, the primary and all secondary efficacy end point analyses met statistical significance from the first assessment and were sustained throughout. Complete terminal complement inhibition was sustained through 26 weeks in all patients. Treatment-emergent adverse events were all mild/moderate and predominantly unrelated to eculizumab.
Conclusions: Eculizumab was effective in reducing disease burden and was well tolerated in adolescents with refractory AChR antibody-positive gMG.
Keywords: AChR Ab+ gMG; Adolescents; Eculizumab; Generalized myasthenia gravis; Phase 3.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Dr. Brandsema has received research funding from Alexion, AstraZeneca Rare Disease, Momenta/Janssen, and Argenx; individual consulting fees from Momenta/Janssen and Argenx; and support in attending meetings from Alexion, AstraZeneca Rare Disease. Dr. Ginsberg reports that Alexion, AstraZeneca Rare Disease, sponsored the current research and associated costs including the provision of equipment needed for the conduct of the study. Dr. Rao has received research funding from Alexion, AstraZeneca Rare Disease, and NS Pharma; individual consulting fees from Biogen, AveXis/Novartis, Genentech/Roche, Sarepta Therapeutics, NS Pharma, Scholar Rock, PTC Therapeutics, and Regenxbio; honoraria from Biogen, AveXis/Novartis, Genentech/Roche, PTC therapeutics, France Foundation, and the Muscular Dystrophy Association; travel assistance from Cure SMA, NS Pharma, Biogen, AveXis/Novartis, and France Foundation, Neuropedicon; honoraria for attending advisory boards or data safety meetings from Capricor and Watermark, and expert testimony fees. Dr. Ruzhansky has received research funding from Argenx, Alexion, AstraZeneca Rare Disease, Alnylam, Corbus, UCB/Ra, Momenta Janssen, MGNet, and the Myasthenia Gravis Foundation of America; individual consulting fees from Guidepoint and GLG; honoraria from WebMD; support in attending meetings from MUSC and MGNet; and honoraria for attending advisory boards or data safety meetings from Argenx, Alexion, AstraZeneca Rare Disease, Amylyx, Immunovant, UCB/Ra, and Guidepoint. Dr. Suresh has received payment for speaking from Takeda Pharmaceuticals and for participating in advisory boards or data safety meetings from Alexion, AstraZeneca Rare Disease, and Argenx. Dr. Howard has received research support (paid to his institution) from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Cartesian Therapeutics, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Myasthenia Gravis Foundation of America, the Muscular Dystrophy Association, the National Institutes of Health (including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), PCORI, Ra Pharmaceuticals (now UCB Pharma), and Takeda Pharmaceuticals; honoraria from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Immunovant Inc, Ra Pharmaceuticals (now UCB Pharma), Regeneron Pharmaceuticals, Sanofi US, and Viela Bio Inc (now Horizon Therapeutics); and nonfinancial support from Alexion, AstraZeneca Rare Disease, Argenx, BVBA, Ra Pharmaceuticals (now UCB Pharma), and Toleranzia AB. Drs. Frick, Hicks, and Liao are employees of and own stock in Alexion, AstraZeneca Rare Disease. No other disclosures were reported.
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