STUDY DESIGNS
ZILBRYSQ was studied in a Phase 3 pivotal trial and extension study
RAISE: Phase 3 study included adult patients with mild to severe anti-AChR Ab+ gMG1
The efficacy and safety of ZILBRYSQ for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive (Ab+) were established in a 12-week, multicenter, randomized, double-blind, placebo-controlled study.
- A total of 174 patients were randomized to receive either ZILBRYSQ (n=86) or placebo (n=88)
- Patients on concomitant medications to treat gMG continued on therapy at stable doses throughout the course of the study
RAISE study design1
Primary Endpoint at Week 12:
- Change from baseline (CFB) in MG-Activities of Daily Living (MG-ADL) total score
Select Secondary Endpoints at Week 12:
- CFB in Quantitative Myasthenia Gravis (QMG) score
- CFB in Myasthenia Gravis Composite (MGC) score
- CFB in Myasthenia Gravis Quality of Life-15 revised (MG-QoL 15r) score
- Diagnosis of mild to severe gMG (Myasthenia Gravis Foundation of America clinical classification class II to IV)
- Positive serology for AChR-binding autoantibodies
- MG-ADL total score of ≥6
- Those on MG therapy prior to screening needed to maintain a stable dose (includes acetylcholinesterase [AChE] inhibitors, steroids, or non-steroidal immunosuppressive therapies [NSISTs], either in combination or alone)
Exclusion criteria included1:
- Those who had had a thymectomy within 12 months before baseline or were scheduled to have one during the 12-week study
- Those who had received treatment with intravenous immunoglobulin, subcutaneous immunoglobulin, or plasma exchange within 4 weeks before baseline
A participant was considered treatment refractory if they had treatment for at least 1 year with 2 or more of the following therapies: prednisone, azathioprine, mycophenolate, cyclosporine, cyclophosphamide, methotrexate, tacrolimus, rituximab, eculizumab, or other corticosteroids; or a history of treatment with at least 1 of these therapies for 1 year or more and required chronic plasma exchange, intravenous immunoglobulin, or subcutaneous immunoglobulin at least every 3 months for the 12 months before enrollment.
Safety set, includes all participants who received at least 1 dose of study drug with participants analyzed based on the study treatment received.
RAISE-XT: an extension study of adult patients who opted to continue on ZILBRYSQ or switch to ZILBRYSQ from placebo3,4
The primary objective of RAISE-XT was to evaluate the long-term safety and tolerability of ZILBRYSQ in study participants with gMG. Long-term efficacy was also studied through multiple measures as secondary endpoints.
RAISE-XT: extension study‡
RAISE-XT evaluated 200 patients from either Phase 2 or 3, including 17 patients from Phase 2 who started with or switched to 0.1 mg/kg. The graphic above shows only the patients continuing or switching to ZILBRYSQ at the approved dosage (0.3 mg/kg) and are solely represented in the subsequent analyses on efficacy.3,4
At the time of data cutoff (November 11, 2023), most patients who entered RAISE-XT (73%) were still enrolled, with no discontinuations reported by the investigators as being due to lack of efficacy.5
This open-label extension is an ongoing study with the current interim data cut at Week E108 (November 11, 2023).5
Primary Endpoint3:
- Incidence of treatment-emergent adverse events
Select Secondary Endpoints at Week E123:
- CFB in MG-ADL score
- CFB in QMG score
- CFB in MGC score
- CFB in MG-QoL 15r score
References:
- Howard JF Jr, Bresch S, Genge A, et al; RAISE Study Team. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, Phase 3 study. Lancet Neurol. 2023;22(5):395-406. doi:10.1016/S1474-4422(23)00080-7
- ZILBRYSQ [Prescribing Information]. Smyrna, GA: UCB, Inc.
- Howard JF Jr, Bresch S, Farmakidis C, et al. Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study. Ther Adv Neurol Disord. 2024;17(3):1-16. doi:10.1177/17562864241243186
- Howard JF Jr, Freimer M, Genge A, et al. Response rates with zilucoplan in generalised myasthenia gravis: 120-week interim analysis of RAISE-XT. Presented at: International Congress on Neuromuscular Diseases; October 25-29, 2024; Perth, Australia. Session OS.03.06.
- Howard JF Jr, Freimer M, Genge A, et al; on behalf of the RAISE-XT Study Team. Long-term safety and efficacy of zilucoplan in generalized myasthenia gravis: 120-week interim analysis of RAISE-XT. Poster presented at: American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting; October 15-18, 2024; Savannah, GA. Poster 192.
