Final CHAMPION MG Trial Data Show Sustained Benefit, Safety of Ravulizumab in Myasthenia Gravis

Author(s):

Isabella Ciccone, MPH

Fact checked by:

Marco Meglio

Key Takeaways

Ravulizumab demonstrated sustained efficacy and safety in treating generalized myasthenia gravis over a median of 759 days, with significant improvements in MG-ADL scores.
Both original ravulizumab and placebo-switch groups showed improvements, with 88.1% achieving at least a 2-point MG-ADL score improvement.
Additional outcome measures, including QMG and quality of life scores, showed parallel gains, with reduced corticosteroid use over time.
Limitations include the absence of a placebo group during the open-label extension and potential data collection issues during the COVID-19 pandemic.

Results from the open-label extension of a phase 3 trial showed that treatment with ravulizumab sustained clinical benefits for up to 4 years in patients with generalized myasthenia gravis.

Tuan Vu, MD

(Credit: LinkedIn)

Newly published in the European Journal of Neurology, final results from the open-label extension of the phase 3 CHAMPION MG trial (NCT03920293) assessing ravulizumab (Ultomiris; AstraZeneca) revealed treatment with the agent demonstrated durable efficacy and continued safety in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis (MG).¹

These long-term data build on previous findings from the randomized controlled and interim open-label phases of the study testing ravulizumab in MG, with data showing sustained improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores and other key clinical measures over up to 4 years of treatment. Among all ravulizumab-treated patients (n = 169), 161 continued into the open-label extension, with a median treatment duration of 759 days.

Patients in both treatment groups, those who continued ravulizumab from the controlled phase (n = 78) and those who switched from placebo (n = 83), showed improvements on MG-ADL scores. At week 164, MG-ADL total scores in the ravulizumab-treated group improved by least squares mean of –4.0 (95% CI, –5.3 to –2.8; P <.0001) from randomized controlled period baseline. In the placebo-treated group, authors noted that a mean change of –2.1 (95% CI, –3.3 to –0.9; P = .0005) was observed from OLE baseline after 138 weeks.

These results were also presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, by lead author Tuan Vu, MD, professor of neurology at the University of South Florida Morsani College of Medicine, and director for Neuromuscular Medicine and EMG.² Overall, 88.1% of patients achieved at least a 2-point improvement in MG-ADL scores (n = 141), and among those, 41.8% reached a score of 0 or 1 (n = 59). More than half of these patients (n = 32; 54.2%) maintained this low symptom status for over half of their remaining study duration.

All told, parallel gains were reported in other outcome measures, including Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Quality of Life-15 revised, and Neurological Quality of Life Fatigue subscale scores. The rate of clinical deterioration events was reported as lower in the OLE compared with placebo in the randomized controlled phase. Additionally, authors noted that corticosteroid use decreased over time and that ravulizumab continued to show a favorable safety profile throughout the extension phase, with no meningococcal infections reported.

A key limitation may be the absence of a placebo group during the OLE; however, both patients and investigators remained blinded to the original randomized treatment assignments throughout this phase. It could also be important to note that changes to the collection of QMG scores during the COVID-19 pandemic may have influenced results, as assessments could not be conducted by phone. Additionally, 17 patients who required rescue therapy were included in the analysis, which may have negatively affected the observed efficacy outcomes.

Ravulizumab, a complement C5 inhibitor, was first approved as a treatment for patients with generalized MG in 2022 based on data from CHAMPION-MG, and later had its indication expanded to include patients with neuromyelitis optica spectrum disorder in 2024. It is also approved in the US as a treatment for adults and children 1 month and older with paroxysmal nocturnal hemoglobinuria.

REFERENCES
1. Vu TH, Mantegazza R, Annane D, et al. Long-Term Efficacy and Safety of Ravulizumab in Adults With Anti-Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: Final Results From the Phase 3 CHAMPION MG Open-Label Extension. Eur J Neurol. 2025;32(4):e70158. doi:10.1111/ene.70158
2. Vu T, Mantegazza R, Annane D, et al. Long-term Efficacy and Safety of Ravulizumab, a Long-acting Terminal Complement Inhibitor, in Adults with Anti-acetylcholine Receptor Antibody-positive Generalized Myasthenia Gravis: Final Results from the Phase 3 CHAMPION MG Open-label Extension. Presented at: 2024 AAN Annual Meeting; April 13-18; S15.010