Efficacy of Rozanolixizumab in Generalized Myasthenia Gravis: Subgroup Analyses from the Randomized Phase 3 MycarinG Study
Tuan Vu1, Artur Drużdż2, Julian Grosskreutz3, Ali A. Habib4, Henry J. Kaminski5, Renato Mantegazza6, Kimiaki Utsugisawa7, John Vissing8, Raphaelle Beau-Lejdstrom9, Marion Boehnlein10, Teresa Gasalla11, Fiona Grimson12, Thaïs Tarancón13, Vera Bril14
1Department of Neurology, University of South Florida Morsani College of Medicine, 2Department of Neurology, Municipal Hospital Poznań, 3Precision Neurology, Department of Neurology, University of Lübeck, 4MDA ALS and Neuromuscular Center, University of California, 5George Washington University, 6Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, 7Department of Neurology, Hanamaki General Hospital, 8Department of Neurology, Rigshospitalet, University of Copenhagen, 9UCB Pharma, Bulle, Switzerland, 10UCB Pharma, Monheim, Germany, 11UCB Pharma, Morrisville, NC, USA, 12UCB Pharma, Slough, UK, 13UCB Pharma, Madrid, Spain, 14University Health Network
Objective:
To establish the efficacy of rozanolixizumab in patients with generalized myasthenia gravis (gMG) across subgroups of prior therapy and disease severity/duration.
Background:
gMG is an autoimmune disorder leading to unpredictable muscle weakness and fatigue. Rozanolixizumab, a humanized IgG4 monoclonal antibody, inhibits FcRn, reducing IgG and pathogenic IgG autoantibody levels.
Design/Methods:
The randomized, double-blind, placebo-controlled, Phase 3 MycarinG study (MG0003/NCT03971422) recruited patients aged ≥18 years with MGFA Class II–IVa AChR or MuSK autoantibody-positive gMG. Patients were randomized 1:1:1 to weekly subcutaneous rozanolixizumab 7mg/kg, 10mg/kg or placebo for 6 weeks. The primary endpoint was least-squares mean (LSM) change from baseline (CFB) to Day 43 in MG-ADL score. Post hoc subgroup analyses included number of prior myasthenia gravis therapies (excluding acetylcholinesterase inhibitors), baseline disease severity and disease duration. Treatment-emergent adverse events (TEAEs) in the overall population were also assessed.
Results:
Patients (N=200) were randomized to rozanolixizumab 7mg/kg (n=66), 10mg/kg (n=67) or placebo (n=67). In the overall population, LSM CFM at Day 43 was –3.4, –3.4 and –0.8 for rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg and placebo, respectively. Mean observed CFB in MG-ADL at Day 43 was more reduced in both rozanolixizumab groups than in the placebo group in the following subgroups: ≥1 prior therapy (n=163): −3.2, −3.3 and −1.0 for rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg and placebo, respectively; ≥2 prior therapies (n=84): −2.5, −3.0 and −0.8; baseline QMG ≤15 (n=110): −3.7, −2.6 and −0.6; baseline QMG >15 (n=90): −3.0, −4.0 and −0.7; baseline disease duration <4 years (n=78): −2.9, −3.1 and −0.6; baseline disease duration ≥4 years (n=122): −3.8, −3.3 and −0.7. TEAEs occurred in 52 (81.3%), 57 (82.6%) and 45 (67.2%) of patients for rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg and placebo, respectively; most were mild or moderate.
Conclusions:
Rozanolixizumab treatment demonstrated greater reductions in MG-ADL score than placebo in a broad range of patients with gMG. Funding: UCB Pharma.