| Title: |
Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study |
| Authors: |
Howard, J.F.; Bresch, S.; Farmakidis, C.; Freimer, M.; Genge, A.; Hewamadduma, C.; Hinton, J.; Hussain, Y.; Juntas-Morales, R.; Kaminski, H.J.; Maniaol, A.; Mantegazza, R.; Masuda, M.; Nowak, R.J.; Sivakumar, K.; Śmiłowski, M.; Utsugisawa, K.; Vu, T.; Weiss, M.D.; Zajda, M.; Bloemers, J.; Boroojerdi, B.; Brock, M.; de la Borderie, G.; Duda, P.W.; Vanderkelen, M.; Leite, M.I. |
| Publisher Information: |
SAGE Publications |
| Publication Year: |
2024 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. Design: Ongoing, multicenter, phase III open-label extension (OLE) study. Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11–4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (n = 52, 26%) and COVID-19 (n = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline −6.06 [−7.09, −5.03]) and were sustained through to Week 60 (−6.04 [−7.21, −4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (−6.46 [−8.19, −4.72]), and were sustained through to Week 60 (−6.51 [−8.37, −4.65]). Consistent results were observed in other efficacy endpoints. Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
1756-2864 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/211729/1/howard-et-al-2024-long-term-safety-and-efficacy-of-zilucoplan-in-patients-with-generalized-myasthenia-gravis-interim.pdf; Howard, J.F. orcid.org/0000-0002-7136-8617 , Bresch, S., Farmakidis, C. et al. (24 more authors) (2024) Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study. Therapeutic Advances in Neurological Disorders, 17. ISSN: 1756-2864 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/211729/ |
| Rights: |
cc_by_nc_4 |
| Accession Number: |
edsbas.698F6234 |
| Database: |
BASE |