Patients With Generalized Myasthenia Gravis Demonstrate Rapid Response Following Ravulizumab Treatment

Author(s):

Luke Halpern, Assistant Editor

Utilizing data from the CHAMPION MG trial, investigators found that many patients had responded to ravulizumab and returned to daily activities within 2 weeks.

In many patients with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG), ravulizumab (Ultomiris; Alexion Pharmaceuticals Inc) led to a rapid response within multiple weeks, according to results from a recent analysis published in European Journal of Neurology.¹

Picture of a person with highlighted neuromuscular junction showing dysfunction, experiencing muscle weakness and fatigue

Myasthenia gravis can cause muscle weakness and fatigue. | Image Credit: © Lila Patel | stock.adobe.com

Ravulizumab, a terminal complement C5 inhibitor, was examined as a potential treatment in patients with AChR Ab+ gMG in the CHAMPION MG study (NCT03920293), a 26-week randomized and placebo-controlled trial of 175 patients. The magnitude of mean changes from baseline to week 26 in patient-reported Myasthenia Gravis-Activities of Daily Living [MG-ADL] scale was significantly increased in patients receiving ravulizumab compared with placebo.^2,3

This current, post-hoc analysis sought to assess the timing of response to ravulizumab regarding patients’ functional abilities and muscle strength, utilizing data from the CHAMPION MG study. Of interest was the onset of response when compared with treatments for serious presentations of gMG, such as intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) therapy.^1,4

The investigators used generally accepted thresholds for minimal clinically important difference (MCID) for improvement of a 2-point reduction in MG-ADL score and a 3-point reduction in Quantitative Myasthenia Gravis (QMG) total score. In total, the analyzed population comprised 134 patients who, at the time of ravulizumab initiation, had available data indicating an MG-ADL score of ≥ 6.¹

The median time to first MG-ADL response in patients receiving ravulizumab, based on a definition of ≥ 2-point reduction in total score, was 2.1 (95% CI, 2.1-2.6 weeks). After 2 weeks of treatment, the cumulative MG-ADL response rate was 58%; following 26 weeks, it was 86%, and at data cut-off, it was 88%. Similarly rapid responses were observed in the analysis based on a ≥ 3-point reduction in total MG-ADL score.¹

Regarding QMG responses, the median time to first QMG response, based on a ≥ 3-point reduction in total QMG score, for patients receiving ravulizumab was 4.1 (95% CI, 2.1-10.0) weeks. Cumulative QMG response rates were 46% following 2 weeks of treatment, 75% after 26 weeks, and 86% at the data cut-off point, according to the investigators. Responses were not as rapid when a more stringent ≥ 5-point reduction in QMG score was used as the analysis threshold.¹

About the Trial

Trial Name: Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis

ClinicalTrials.gov ID: NCT03920293

Sponsor: Alexion Pharmaceuticals, Inc

Completion Date: May 25, 2023

Ravulizumab demonstrated its ability to rapidly improve the quality of life for patients with AChR Ab+ gMG, with many reporting improvements in QMG and MG-ADL scores within 2 weeks. This onset can be compared with those of treatments for serious gMG. Guptill et al, in their analysis of emerging gMG therapies, discussed how IVIG and PLEX are often-used treatments for acute severe exacerbations of gMG.⁴

As both sets of authors explain, PLEX has a rapid onset of action—often within a few days—while IVIG’s response is usually more modest, within a slightly longer time period. Critically, these treatments are typically administered for short periods of time, only to control severe MG or acute exacerbations. Ravulizumab’s effectiveness and quick onset to response for generalized disease is notable when compared with treatments for more serious disease presentations.^1,4

The data garnered from this analysis can assist decision-makers in what the appropriate duration of ravulizumab should be, depending on the patient. Some limitations of the analysis were reported by the investigators, including the low patient numbers in some of the response groups and its post hoc nature. Overall, the investigators were limited in this regard because of their use of data being restricted to the CHAMPION MG trial.^1,2

“Further work to evaluate patient and disease characteristics that predict response and timing of response would be beneficial,” the investigators concluded.¹

REFERENCES

1. Habib AA, Benatar M, Vu T, et al. Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Eur J Neurol. 2024 00:e16490. doi:10.1111/ene.16490

2. Vu T, Meisel A, Mantegazza R, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evid. 2022;1(5). doi:10.1056/EVIDoa2100066.

3. ClinicalTrials.gov. Safety and efficacy study of ravulizumab in adults with generalized myasthenia gravis. National Library of Medicine. Updated May 28, 2024. Accessed October 22, 2024. https://clinicaltrials.gov/study/NCT03920293

4. Guptill JT, Soni M, Meriggioli MN, et al. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. Neurotherapeutics. 2016;13(1):118-131. doi:10.1007/s13311-015-0398-y