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Clinical Trial
. 2025 Mar 19;272(4):275.
doi: 10.1007/s00415-025-12958-9.

Safety and efficacy of chronic weekly rozanolixizumab in generalized myasthenia gravis: the randomized open-label extension MG0004 study

Vera Bril  1 , Artur Drużdż  2 , Julian Grosskreutz  3 , Ali A Habib  4 , Henry J Kaminski  5 , Renato Mantegazza  6 , Sabrina Sacconi  7 , Kimiaki Utsugisawa  8 , Tuan Vu  9 , Marion Boehnlein  10 , Maryam Gayfieva  11 , Bernhard Greve  10 , Franz Woltering  10 , John Vissing  12 ; MG0004 study investigators
Collaborators, Affiliations
Clinical Trial

Safety and efficacy of chronic weekly rozanolixizumab in generalized myasthenia gravis: the randomized open-label extension MG0004 study

Vera Bril et al. J Neurol. .

Abstract

Background: In the Phase 3 MycarinG study (NCT03971422), six once-weekly subcutaneous infusions of rozanolixizumab significantly improved myasthenia gravis (MG)-specific outcomes versus placebo in patients with acetylcholine receptor or muscle-specific tyrosine kinase autoantibody-positive generalized MG (gMG). Following completion of MycarinG, patients could enroll in the open-label extension MG0004 study (NCT04124965) to receive chronic weekly rozanolixizumab.

Methods: Patients were re-randomized 1:1 to once-weekly rozanolixizumab 7 or 10 mg/kg for up to 52 infusions. The primary endpoints were the occurrence of treatment-emergent adverse events (TEAEs) and TEAEs leading to rozanolixizumab discontinuation. After ≥6 visits/infusions patients could switch to the MG0007 study (NCT04650854) to receive cyclic rozanolixizumab treatment.

Results: In MG0004, 70 patients received rozanolixizumab 7 mg/kg (n = 35) or 10 mg/kg (n = 35). Mean treatment duration was 22.9 and 23.7 weeks, respectively, due to rollover into MG0007. TEAEs were reported in 60/70 (85.7%) patients; most were mild/moderate. The most frequently reported TEAEs were headache (25/70 [35.7%]), diarrhea (13/70 [18.6%]) and decreased blood immunoglobulin G (11/70 [15.7%]). There were no opportunistic, serious or severe infections, serious or severe hypersensitivity or injection-site reactions, any anaphylactic reactions or albumin or lipid abnormalities. Maximum mean reduction from baseline in MG Activities of Daily Living score was 3.1 in the 7 mg/kg group and 4.1 in the 10 mg/kg group.

Conclusion: Chronic weekly rozanolixizumab for up to 52 infusions was generally well tolerated, and clinically relevant improvements across MG-specific outcomes were maintained, supporting the long-term use of rozanolixizumab in patients with gMG.

Trial registration: NCT04124965 (registered October 11, 2019).

Keywords: FcRn inhibitor; Myasthenia gravis; Phase 3 clinical trial; Rozanolixizumab.

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Conflict of interest statement

Declarations. Ethical approval: The study protocol, amendments, and study participant informed consent were approved by a national, regional or independent ethics committee or institutional review board. All patients provided written informed consent. The study was conducted in accordance with local regulations, the International Conference on Harmonization Good Clinical Practice requirements, and the principles of the Declaration of Helsinki. Conflicts of interest: V. Bril is a Consultant for Akcea, Alexion Pharmaceuticals, Alnylam, argenx, CSL, Grifols, Immunovant, Ionis, Janssen Pharmaceuticals (now Johnson & Johnson Innovative Medicine), Momenta (now Johnson & Johnson), Novo Nordisk, Octapharma, Pfizer, Powell Mansfield, Roche, Sanofi, Takeda Pharmaceuticals and UCB. She has received research support from Akcea, Alexion Pharmaceuticals, argenx, CSL, Grifols, Immunovant, Ionis, Momenta (now Johnson & Johnson), Octapharma, Takeda Pharmaceuticals, UCB and Viela Bio (now Amgen). A. Drużdż has nothing to disclose. J. Grosskreutz has served as a Consultant for Alexion Pharmaceuticals, Biogen and UCB, and his institution has received research support from the Boris Canessa Foundation. A.A. Habib has received research support from Alexion Pharmaceuticals, argenx, Cabaletta Bio, Genentech/Roche, Immunovant, Regeneron Pharmaceuticals, UCB and Viela Bio (now Amgen). He has received honoraria from Alexion Pharmaceuticals, Alpine Immune Sciences, argenx, Genentech/Roche, Immunovant, Inhibrx, NMD Pharma, Regeneron Pharmaceuticals and UCB. H.J. Kaminski is a Consultant for Cabaletta Bio, Lincoln Therapeutics, Roche, Takeda Pharmaceuticals and UCB, and is CEO and CMO of ARC Biotechnology, LLC based on US Patent 8,961,98. He is Principal Investigator of the Rare Disease Network for Myasthenia Gravis (MGNet) National Institute of Neurological Disorders & Stroke, U54 NS115054, and Targeted Therapy for Myasthenia Gravis. He has received R41 NS110331-01 to ARC Biotechnology. R. Mantegazza has received funding for travel and meeting attendance or advisory board participation from Alexion Pharmaceuticals, argenx, BioMarin, Catalyst, Sanofi, Regeneron Pharmaceuticals Sanofi and UCB. S. Sacconi has nothing to disclose. K. Utsugisawa has served as a paid Consultant for argenx, Chugai Pharmaceutical, HanAll Biopharma, Janssen Pharmaceuticals (now Johnson & Johnson Innovative Medicine), Merck, Mitsubishi Tanabe Pharma, UCB and Viela Bio (now Amgen); he has received speaker honoraria from Alexion Pharmaceuticals, argenx, the Japan Blood Products Organization and UCB. T. Vu is the USF Site Principal Investigator for MG clinical trials sponsored by Alexion/AstraZeneca Rare Disease, Amgen, argenx, Cartesian Therapeutics, COUR Pharmaceuticals, Dianthus Therapeutics, Immunovant, Johnson & Johnson, NMD Pharma, Regeneron Pharmaceuticals and UCB, and has served as a speaker for Alexion/AstraZeneca Rare Disease, argenx and CSL Behring. He performed consulting work for Alexion/AstraZeneca Rare Disease, argenx, Dianthus Therapeutics, ImmunAbs and UCB. M. Boehnlein is an employee and shareholder of UCB. M. Gayfieva is a former employee and shareholder of UCB. B. Greve is an employee and shareholder of UCB. F. Woltering is an employee and shareholder of UCB. J. Vissing has been a Consultant on advisory boards for Amicus Therapeutics, Biogen, Edgewise Therapeutics, Fulcrum Therapeutics, Genethon, Horizon Therapeutics (now Amgen), Lupin, ML Biopharma, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi Genzyme (now Sanofi), Sarepta Therapeutics and UCB. He has received research, travel support and/or speaker honoraria from Alexion Pharmaceuticals, argenx, Biogen, Edgewise Therapeutics, Fulcrum Therapeutics, Lupin, Sanofi Genzyme (now Sanofi) and UCB. He is a Principal Investigator in clinical trials for Alexion Pharmaceuticals, argenx, Atamyo Therapeutics, Genethon, Horizon Therapeutics (now Amgen), Janssen Pharmaceuticals (now Johnson & Johnson Innovative Medicine), ML Biopharma, Novartis, Regeneron Pharmaceuticals, Roche, Sanofi Genzyme (now Sanofi) and UCB.

Figures

Fig. 1
Fig. 1
Patient flow. AE adverse event
Fig. 2
Fig. 2
Mean change from baseline to Week 60 in a MG-ADL, b MGC and c QMG scores (safety set). Safety set by first dose received. The light gray area represents study visits at which patient numbers were low (≤10 per treatment group at any scheduled assessment). BL baseline, CFB change from baseline, MG-ADL Myasthenia Gravis Activities of Daily Living, MGC Myasthenia Gravis Composite, QMG Quantitative Myasthenia Gravis, SE standard error
Fig. 2
Fig. 2
Mean change from baseline to Week 60 in a MG-ADL, b MGC and c QMG scores (safety set). Safety set by first dose received. The light gray area represents study visits at which patient numbers were low (≤10 per treatment group at any scheduled assessment). BL baseline, CFB change from baseline, MG-ADL Myasthenia Gravis Activities of Daily Living, MGC Myasthenia Gravis Composite, QMG Quantitative Myasthenia Gravis, SE standard error
Fig. 3
Fig. 3
Mean change from baseline to Week 60 in MG Symptoms PRO scale scores: a Muscle Weakness Fatigability, b Physical Fatigue and c Bulbar Muscle Weakness (safety set). Safety set by first dose received. The light gray area represents study visits at which patient numbers were low (≤10 per treatment group at any scheduled assessment). BL baseline, CFB change from baseline, MG myasthenia gravis, PRO patient-reported outcome; SE, standard error
Fig. 3
Fig. 3
Mean change from baseline to Week 60 in MG Symptoms PRO scale scores: a Muscle Weakness Fatigability, b Physical Fatigue and c Bulbar Muscle Weakness (safety set). Safety set by first dose received. The light gray area represents study visits at which patient numbers were low (≤10 per treatment group at any scheduled assessment). BL baseline, CFB change from baseline, MG myasthenia gravis, PRO patient-reported outcome; SE, standard error
Fig. 4
Fig. 4
Median percentage change from baseline in total IgG (safety set). Safety set by the first dose received. Mean (SD) total IgG at baseline was 9.06 (3.16) g/L in the rozanolixizumab 7 mg/kg group and 8.78 (2.62) g/L in the rozanolixizumab 10 mg/kg group. The lowest mean (SD) total IgG during treatment was 2.55 (1.39) g/L at Week 17 in the rozanolixizumab 7 mg/kg group and 2.23 (1.00) g/L at Week 5 in the rozanolixizumab 10 mg/kg group. The light gray area represents study visits at which patient numbers were low (≤10 per treatment group at any scheduled assessment). BL baseline, IgG immunoglobulin G, SD standard deviation
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