Michael Weiss, MD, Neurologist at the University of Washington, discusses data on the RAISE and RAISE-XT clinical trials of zilucoplan for the treatment of generalized myasthenia gravis (gMG).
gMG is a chronic autoimmune neuromuscular disease characterized by weakness of the skeletal muscles. Common symptoms include weakness of the muscles that control the eye and eyelid, facial expressions, chewing, talking, and swallowing. The condition results from a defect in the transmission of nerve impulses to muscles, which is due to the presence of antibodies against acetylcholine. The exact reason this occurs is not known.
Zilucoplan and the RAISE Clinical Trial Program
Data on the RAISE and RAISE-XT clinical trials of zilucoplan for the treatment of generalized MG was recently presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting and Myasthenia Gravis Foundation of American (MDFA) Scientific Session.
Zilucoplan is a once-daily SC injection, self-administered peptide inhibitor of complement component 5 (C5 inhibitor). Zilucoplan may inhibit complement-mediated damage to the neuromuscular junction through its targeted mechanism of action. The treatment was approved by the U.S. Food and Drug Administration in October 2023 for the treatment of adult patients with AChR-positive gMG.
The RAISE clinical trial (NCT04115293) was a multicenter, randomized, double-blind, placebo-controlled, study evaluating the safety, efficacy, and tolerability of zilucoplan in patients with generalized MG. RAISE-XT (NCT04225871) is a phase 3, multicenter, open-label extension study of zilucoplan in patients with generalized MG.
Effect of Zilucoplan on Fatigue in Patients With gMG: RAISE-XT 120-Week Follow-Up
The RAISE clinical trial demonstrated that treatment with zilucoplan resulted in clinically meaningful and nominally significant improvement in fatigue versus placebo in patients with gMG. The objective of this post hoc analysis was to assess the long term effect of zilucoplan in the ongoing RAISE-XT extension study up to week 120.
At week 120, the mean change from baseline in the Neuro-QoL Short Form Fatigue T-score was 12.65. Of patients with available data at baseline and week 120, 77% showed clinicallt meaningful improvements in their T-score at week 120 compared to baseline. Additionally, 60.7% transitioned to a lower fatigue severity level. At week 120, 60.7% of patients had mild or no fatigue compared with 19.7% at baseline.
Long-Term Effectiveness of Zilucoplan in MG: Predictive Modeling in a United States Real-World Database
The objective of this study was to estimate the long-term effect of zilucoplan on the risk of severe exacerbations using predictive modeling based on clinical trial data and a U.S. real-world database. It assessed the medical benefit of zilucoplan on top of standard of care and its impact across different gMG therapy scenarios.
Step one included replication of most RAISE inclusion/exclusion criteria in the external control arm and weighting it with the zilucoplan arm. This resulted in a strong similarity in baseline patient characteristics. The adjusted hazard ratio of zilucoplan, compared to standard of care, on severe exacerbations over two years was 0.14.
Additionally, simulations showed 8.6%-15.1% reduction in severe exacerbations risk at two years when using zilucoplan in addition to standard of care versus standard of care alone in different scenarios. This suggests that zilucoplan significantly reduces the long-term risk of severe exacerbations with benefit across different gMG real-world standard of care therapy.
Interpreting Patient Quality of Life Experience With Zilucoplan in gMG in RAISE and RAISE-XT
In the RAISE clinical trial, treatment with zilucoplan resulted in statistically significant improvements in the Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) versus placebo in patients with gMG. The objective of this study was to interpret the meaningfulness of MG-QoL15r improvements.
At Week 12, patients on zilucoplan were more likely than those on placebo to answer “not at all” for all items, including for the most severe symptoms (e.g., for “difficulty speaking”, placebo: 41.9%; zilucoplan: 63.9%). For the total population, this likelihood increased at Week 60.
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To learn more about MG and other rare autoimmune conditions, visit https://checkrare.com/diseases/autoimmune-and-auto-inflammatory-disorders/
