Comparative Efficacy of Zilucoplan Versus Intravenous Immunoglobulin, Eculizumab, and Ravulizumab Using...

Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder which impacts signaling at the neuromuscular junction. While new targeted therapies have emerged, there is no direct comparative evidence. This study aimed to compare the efficacy of zilucoplan with eculizumab, intravenous immunoglobulin (IVIg), and ravulizumab using matching-adjusted indirect comparisons (MAICs).

Phase 3 studies of complement component 5 (C5) inhibitors and IVIg were identified through a literature review. MAICs were conducted for zilucoplan versus IVIg, zilucoplan versus ravulizumab (both comparisons in patients with gMG), and zilucoplan versus eculizumab (in patients with refractory gMG). Propensity score-based weighting methods were used to balance covariates between trial populations. Continuous outcomes were analyzed through linear regression, and dichotomous outcomes were analyzed through logistic regression. Treatment effects were presented as mean differences or odds ratios (ORs) with 95% confidence intervals (CIs). Scenario analyses were performed.

Compared with IVIg, zilucoplan was associated with statistically significant improvements in the Quantitative Myasthenia Gravis score (QMG) at 2 weeks (OR: - 1.95; 95% CI: - 3.50, - 0.39) and 4 weeks (OR: - 3.30; 95% CI: - 4.89, - 1.71). Compared with eculizumab at 24/26 weeks, the MAIC analysis showed statistically significant differences favoring zilucoplan for the MG Activities of Daily Living (MG-ADL) score (OR: - 1.99; 95% CI: - 3.30, - 0.69), the Quantitative Myasthenia Gravis (QMG) score (OR: - 3.23; 95% CI: - 4.63, - 1.82), and the Myasthenia Gravis Composite questionnaire (MGC) (OR: - 4.27; 95% CI: - 6.79, - 1.76) in patients with refractory gMG. Compared with ravulizumab at 24/26 weeks, the MAIC analysis showed statistically significant differences favoring zilucoplan for the MG-ADL (OR: - 2.70; 95% CI: - 3.74, - 1.67), QMG (OR: - 5.72; 95% CI: - 7.02, - 4.43), and the Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r) (OR: - 5.51; 95% CI - 7.63, - 3.38) scores.

In this analysis, zilucoplan was associated with a significantly higher magnitude of clinically meaningful improvement in QMG and MG-ADL scores compared to IVIg and two C5 inhibitors, eculizumab and ravulizumab. In the absence of head-to-head clinical data, these findings provide additional evidence to assist with treatment decisions in this setting.