Advancements in gMG Management: Zilucoplan as an Alternative to C5 Inhibitors

Advancements in gMG Management: Zilucoplan as an Alternative to C5 Inhibitors

The treatment landscape for acetylcholine receptor antibody-positive (AChr) generalized myasthenia gravis (gMG) is evolving, with new data supporting a move from hospital-based intravenous (IV) therapies to self-administered subcutaneous (SC) options.

A recent phase 3b, open-label study published in Therapeutic Advances in Neurological Disorders in July 2025 evaluated the safety, efficacy, and patient experience of switching from eculizumab or ravulizumab to daily SC zilucoplan in adults with stable gMG.

Here’s a quick overview of the study and its findings.

Trial Design

The study enrolled 26 adults with stable AChR autoantibody-positive gMG who had been on eculizumab or ravulizumab for at least three or four months, respectively. Participants transitioned to zilucoplan 0.3 mg/kg SC once daily without a washout period, starting on the day they would have received their next IV dose.

The 12-week study assessed safety as the primary endpoint, functional outcomes via Myasthenia Gravis Activities of Daily Living (MG-ADL) as a secondary endpoint, and patient-reported satisfaction and preference as exploratory endpoints.

Clinical Outcomes

Looking at the results, MG-ADL scores improved significantly across the full cohort by Week 12 (LS mean change: −1.15; p=0.0217), meeting non-inferiority criteria relative to baseline treatment.

Improvements were particularly notable in patients switching from ravulizumab, with MG-ADL (−2.41; p=0.0307) and Quantitative MG (QMG) (−3.52; p=0.0149) scores showing clinically meaningful and statistically significant changes.

Approximately 75% of patients experienced stable or improved symptoms by both MG-ADL and QMG metrics.

Interestingly, baseline complement inhibition was lower in ravulizumab switchers, likely due to the longer eight-week dosing interval. Zilucoplan restored and maintained greater than 95% complement inhibition by week two, consistent with its pharmacodynamic profile and daily dosing.

Safety Profile

Treatment-emergent adverse events (TEAEs) were reported in 73.1% of patients, most being mild. Severe TEAEs were limited to injection-site reactions and transient lab abnormalities.

Only two patients discontinued due to adverse events, including one case of reactivated Epstein–Barr virus, deemed unrelated to treatment. There were no deaths and no cases of meningococcal infection occurred.

Patient-Centered Insights

Patient preference strongly favored zilucoplan. By week 12, 76.9% of participants preferred SC over IV administration, likely driven by convenience, reduced travel, and shorter administration time. 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores showed marked improvements in global satisfaction (+19.4), effectiveness (+13.9), and convenience (+21.7) domains, all surpassing thresholds for meaningful change.

Among those switching from eculizumab, the convenience domain improved most (likely reflecting eculizumab's biweekly schedule), while ravulizumab switchers saw greater gains in perceived effectiveness, possibly reflecting perceived waning efficacy near the end of the eight-week cycle.

Implications for Clinical Practice

While the study’s size and duration limit broader generalization, it aligns with previous RAISE and RAISE-XT data demonstrating long-term safety and sustained efficacy of zilucoplan over 60 weeks. Its room-temperature stability for up to three months further strengthens its role as a home-based option.

For neurologists and care teams, these results support zilucoplan as a flexible and patient-centered alternative for individuals already stabilized on IV complement inhibitors. The switch can occur without washout, preserves complement blockade, and may even enhance disease control in select subgroups.

Reference
Freimer M, Desai U, Govindarajan R, et al. Switching to subcutaneous zilucoplan from intravenous complement 5 inhibitors in generalised myasthenia gravis: A phase IIIb, open-label study. Ther Adv Neurol Disord. 2025:18:17562862451347283. doi:10.1177/17562864251327283