RAISE-XT: An interim analysis of safety and efficacy in an open-label extension study of zilucoplan in patients with myasthenia gravis
Miriam Freimer1, M. Isabel Leite2, Angela Genge3, Yessar Hussain4, Henry J. Kaminski5, Renato Mantegazza6, Kimiaki Utsugisawa7, Tuan Vu8, Petra W. Duda9, Babak Boroojerdi10, Mark Vanderkelen11, Romana Lowcock12, James F. Howard Jr.13
1Department of Neurology, The Ohio State University Wexner Medical Center, 2Nuffield Department of Clinical Neurosciences, University of Oxford, 3Clinical Research Unit, The Montreal Neurological Institute, 4Department of Neurology, Dell Medical School, The University of Texas at Austin, 5Department of Neurology & Rehabilitation Medicine, George Washington University, 6Neuroimmunology and Neuromuscular Diseases Department, Fondazione Istituto Neurologico, 7Department of Neurology, Hanamaki General Hospital, 8Department of Neurology, University of South Florida Morsani College of Medicine, 9UCB Pharma, Cambridge, MA, USA, 10UCB Pharma, Monheim, Germany, 11UCB Pharma, Braine L'Alleud, Belgium, 12UCB Pharma, Slough, UK, 13Department of Neurology, The University of North Carolina at Chapel Hill
Objective:
Evaluate the safety and efficacy of zilucoplan in patients with generalized myasthenia gravis (gMG).
Background:
Long-term data from RAISE-XT (NCT04225871), a Phase 3, multicenter, open-label extension study, will enhance our understanding of the safety and efficacy of the C5 inhibitor zilucoplan in patients with gMG.
Design/Methods:
Adults (≥18, <75 years) with gMG who completed a qualifying zilucoplan study (NCT03315130/NCT04115293) self-administered daily subcutaneous injections of zilucoplan 0.3 mg/kg. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from qualifying study baseline to Extension Week 12 (Week E12) in Myasthenia Gravis Activities of Daily Living (MG-ADL) score, responder rates for MG-ADL and Quantitative Myasthenia Gravis (QMG; reduction of ≥3 points and ≥5 points without rescue therapy, respectively), and minimal symptom expression (MSE; MG-ADL 0/1).
Results:
Among 199 patients enrolled in RAISE-XT, 104 continued zilucoplan from their parent study (zilucoplan group) and 95 switched to zilucoplan from placebo (placebo-switch group). Median exposure at data cut-off was 253 days (range 29–1434). TEAEs occurred in 169 (84.9%) patients; 46 (23.1%) patients experienced a serious TEAE. At Week E12, LS mean changes in MG-ADL score for the zilucoplan and placebo-switch groups (after 24 and 12 weeks of zilucoplan, respectively) were −6.30 (95% CI: −7.44, −5.15) and −6.32 (95% CI: −8.00, −4.65). MG-ADL responder rates improved from extension study baseline through Week E12 (zilucoplan: 75.0% to 80.3% of patients; placebo-switch: 52.2% to 79.7%); a similar effect was observed on QMG responder rates. MSE responder rate increased through Week E12 (zilucoplan: 19.6% to 26.8% of patients; placebo-switch: 7.8% to 29.0%).
Conclusions:
In this interim analysis of RAISE-XT, zilucoplan demonstrated a favorable long-term safety profile and sustained efficacy. Responder rates improved from extension study baseline in both the zilucoplan and placebo-switch groups. Funding: UCB Pharma.