Eculizumab Generates High Response Rates in Generalized Myasthenia Gravis


By the end of the open-label extension, 15-17% of patients showed clinically meaningful first response with eculizumab treatment.

James Howard, MD, FAAN

James Howard, MD, FAAN

Analysis of data from the REGAIN study and its open-label extension showed an early high rate of clinical response, maintained over the long-term, in patients with refractory generalized myasthenia gravis (gMG) treated with eculizumab.

By Week 12 and through the open-label extension period’s end, response assessed using Myasthenia Gravis-Activities of Daily Living (MG-ADL) was achieved in 67.3% (n= 66) and 84.7% (n= 83) of patients, respectively. Eculizumab is a humanized monoclonal antibody that specifically binds with high affinity to human terminal complement protein C5.

Findings were presented by James Howard, MD, FAAN, chief, Neuromuscular Disorders Section, and professor of neuromuscular disease, University of North Carolina, during the virtual Clinical Trials Session of the 2020 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference on March 24, 2020.

The research presented was a retrospective analysis of response profiles in the 6-month, double-blind, placebo-controlled REGAIN study (NCT01997229) and its open label extension (NCT02301624), which consisted of a 4-week blind introduction phase, followed by an open-label phase (up to 4 years). In both studies, patients with anti-acetylcholine receptor antibody-positive refractory gMG demonstrated sustained effectiveness while under eculizumab

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Patients who were age >18 years, had an MG-ADL score >6, had Myasthenia Gravis Foundation of America (MFGA) class II-IV disease, had Neisseria meningitidis vaccination, and had therapy administered over the preceding 12 months without symptom control met inclusion criteria.

In REGAIN, patients were randomized to either 900 mg eculizumab weekly (n= 62), 4 times then 1200 mg every 2 weeks or placebo (n= 63). In the open-label extension, participants received 1200 mg eculizumab every 2 weeks starting at week 4 and continued throughout the study.

Response and responder definitions in the retrospective analysis were defined in both MG-ADL and Quantitative Myasthenia Gravis (QMG) scores. An MG-ADL response was defined as a >3-point reduction from baseline, whereas QMG response was >5-point reduction from baseline. Early responders were documented when response was achieved on or before the Week 12 assessment. Late responders were defined as those showed response after the Week 12 assessment while non-responders were those who did not show response to eculizumab treatment up to the end of the open-label extension.

The response analysis data set included 98 patients who received eculizumab, excluding patients who received placebo during REGAIN and had an MG-ADL total score <6 at eculizumab initiation.

In addition to the 67.3% and 84.7% of patients who registered an MG-ADL response by Week 12 and open-label extension end, respectively, QMG response was observed in 56.1% and 71.4% of patients at week 12 and open-label extension end, respectively.

In total, 15.3% (n = 15) of patients did not achieve an MG-ADL response and 28.6% (n = 28) of patients did not achieve a QMG response during the study.

“The findings suggest that although most patients with refractory generalized MG will achieve clinical response (assessed by MG-ADL or QMG scores) by week 12 of eculizumab treatment, first responses can be observed with longer-term treatment,” the study authors wrote.


Howard J, Karam C, Yountz M, O’Brien F, Mozaffar T. Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analysis. Presented at 2020 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference. March 24, 2020. Abstract 55.

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