Efficacy of zilucoplan in patients with generalised myasthenia gravis who have not previously received immunoglobulin or plasma exchange: A subgroup analysis from the Phase 3 RAISE study

Background

RAISE (NCT04115293; N = 174) was a randomised, double-blind, placebo-controlled, Phase 3 study of zilucoplan, a macrocyclic peptide complement component 5 inhibitor, in patients with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalised myasthenia gravis (gMG). Zilucoplan showed clinically meaningful improvements in myasthenia gravis (MG)-specific outcomes versus placebo in the overall population. We assessed the profiles of RAISE patients without and with prior immunoglobulin (intravenous and subcutaneous) or plasma exchange (PLEX) use.

Methods

Adults with anti-AChR Ab+ gMG were randomised 1:1 to daily, self-administered, subcutaneous zilucoplan 0.3 mg/kg or placebo for 12 weeks. The primary efficacy endpoint was change from baseline (CFB) to Week 12 in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. We conducted a prespecified, descriptive analysis of subgroups without and with prior immunoglobulin/PLEX.

Results

At baseline, 54 patients had no prior immunoglobulin/PLEX (zilucoplan: n = 29; placebo: n = 25); this subgroup had experienced milder disease and shorter disease duration from diagnosis than the subgroup with prior immunoglobulin/PLEX. Mean (standard error) CFB in MG-ADL score was −4.22 (0.71) with zilucoplan versus −2.61 (0.50) with placebo in the subgroup without prior immunoglobulin/PLEX, and − 4.93 (0.54) versus −2.94 (0.50) in the subgroup with prior immunoglobulin/PLEX. Zilucoplan was well tolerated with a similar safety profile in both subgroups.

Conclusions

In the RAISE study, patients without prior immunoglobulin/PLEX, who had milder disease, experienced improvements in MG-specific outcomes with zilucoplan that were comparable to those seen in patients with prior immunoglobulin/PLEX. These findings may support early use of zilucoplan in the gMG treatment paradigm.