Response to Rozanolixizumab Across Treatment Cycles in Patients with Generalized Myasthenia Gravis: A Post-hoc Analysis
Robert M. Pascuzzi1, Julian Grosskreutz2, Ali A. Habib3, Zabeen K. Mahuwala4, Renato Mantegazza5, Sabrina Sacconi6, John Vissing7, Tuan Vu8, Raphaёlle Beau Lejdstrom9, Bernhard Greve10, Fiona Grimson11, Thaïs Tarancón12, Vera Bril13
1Neurology Department, Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA, 2Precision Neurology, Department of Neurology, University of Lübeck, Lübeck, Germany, 3MDA ALS and Neuromuscular Center, University of California, Irvine, Irvine, CA, USA, 4Department of Neuromuscular Medicine and Clinical Neurophysiology, University of Kentucky, Lexington, KY, USA, 5Department of Neuroimmunology and Neuromuscular Diseases, Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS, Istituto Nazionale Neurologico Carlo Besta, Milan, Italy, 6Université Côte d'Azur, Peripheral Nervous System & Muscle Department, Université Côte d'Azur, Peripheral Nervous System & Muscle Department, Pasteur 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France, 7Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 8Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, FL, USA, 9UCB Pharma, Bulle, Switzerland, 10UCB Pharma, Monheim, Germany, 11UCB Pharma, Slough, UK, 12UCB Pharma, Madrid, Spain, 13University Health Network, Toronto, ON, Canada
Objective:
To evaluate response to rozanolixizumab over multiple treatment cycles in patients with generalized myasthenia gravis (MG) based on response in Cycle 1.
Background:
In the Phase 3 MycarinG (NCT03971422) study, one cycle (six once-weekly subcutaneous infusions) of rozanolixizumab 7mg/kg or 10mg/kg significantly improved MG-specific outcomes versus placebo. After MycarinG, patients could enroll in open-label extensions (OLEs) MG0004 (NCT04124965) then MG0007 (NCT04650854), or MG0007 directly.
Design/Methods:
MG0004 was an OLE of chronic, once-weekly rozanolixizumab 7mg/kg or 10mg/kg for ≤52 weeks. In MG0007, after an initial six-week cycle (rozanolixizumab 7mg/kg or 10mg/kg), subsequent cycles were administered upon symptom worsening at the investigator’s discretion. Data were pooled across MycarinG, MG0004 (first 6 weeks) and MG0007 (interim analysis; data cut-off: July 08, 2022) for patients with ≥2 symptom-driven cycles. The proportion of patients achieving MG-Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) response (≥2.0-point and ≥3.0-point improvement from baseline, respectively) at Day 43 in each cycle was analyzed. Post-hoc analyses of response rates were conducted based on response to Cycle 1.
Results:
Overall, 127 patients had ≥2 symptom-driven cycles. In Cycle 1, 74.0% (94/127) and 68.5% (87/127) of patients were MG-ADL and QMG responders, respectively, at Day 43. Among MG-ADL Cycle 1 responders, MG-ADL response rates remained high over subsequent cycles (Cycle 2: 78.7% [74/94]; Cycle 3: 77.1% [54/70]; Cycle 4: 78.0% [46/59]). Similar patterns were observed for QMG response among QMG Cycle 1 responders (Cycle 2: 67.4% [58/86]; Cycle 3: 76.2% [48/63]; Cycle 4: 69.2% [36/52]). Of 33 (26.0%) MG-ADL non-responders at Cycle 1, 63.6% (21/33) were responders at Cycle 2. Of 40 (31.5%) QMG non-responders at Cycle 1, 51.3% (20/39) were responders at Cycle 2.
Conclusions:
Patients receiving rozanolixizumab demonstrated a high response rate over multiple cycles irrespective of initial response. Initial non-responders may benefit from additional rozanolixizumab treatment cycles.