Eculizumab Safe and Effective in Adolescents With Myasthenia Gravis, Small-Scale Study Suggests


FDA-approved for adults with generalized myasthenia gravis in 2016, eculizumab continued to show promising efficacy and safety responses in adolescents with the disease, regardless of on concomitant use of IVIG.

John F. Brandsema, MD, pediatric neurologist, Children’s Hospital of Philadelphia

John F. Brandsema, MD

Data from a phase 3, open-label, multicenter study (NCT03759366) of adolescents with myasthenia gravis (MG) showed that treatment with eculizumab (Soliris; Alexion), an FDA-approved terminal complement C5 inhibitor, was safe and effective across a 26-week treatment period.

The trial featured 11 adolescents, aged 12 to 17 years, who were on weight-based dosing regimen of eculizumab and assessed on changes in Quantitative Myasthenia Gravis (QMG) total score. After 26 weeks of therapy, patients experienced least square mean changes of –5.8 (SE, 1.2; P = .0004) for QMG total score and ­–2.3 (SE, 0.6; P = .0017) for Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score.

These data were presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by lead author John F. Brandsema, MD, pediatric neurologist, Children’s Hospital of Philadelphia. During the study, patients had weekly induction of eculizumab, with 1-2 doses of 600 mg or 4 doses of 900 mg, followed by a 2-week maintenance of 300-1200 mg. Six of the 11 individuals were already receiving intravenous immunoglobulin (IVIG) at the beginning of the trial.

Eculizumab was originally approved as a treatment for adults with MG who are anti-acetylcholine receptor antibody-positive in 2016, and later gained FDA greenlight for neuromyelitis optica spectrum disorder in 2019. In the study, similar changes on both QMG and MG-ADL total scores were similar regardless of concurrent IVIG. Each of these analyses met statistical significance after week 1, and sustained that benefit through week 26. Complement inhibition was sustained throughout 26 weeks in all patients.

In terms of safety, all treatment-emergent adverse events (AEs) were mild or moderate in severity and predominantly unrelated to eculizumab. Six serious AEs of MG worsening (n = 3), MG crisis, peritonsillar abscess, and pyrexia, were experienced by 3 patients. Although eculizumab carries a warning label for meningococcal infections, there were none reported during the trial.

The long-term efficacy of eculizumab was previously assessed in the 6-month, double-blind, placebo-controlled REGAIN study (NCT01997229) and its open-label extension (NCT02301624). In REGAIN, adults with MG were randomly assigned 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 (OLE), participants received 1200 mg eculizumab every 2 weeks starting at week 4 and continued throughout the study. In 2021, investigators from REGAIN published a responder analysis of the trial, with early/late responses defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) at less than or greater than 12 weeks, respectively, after eculizumab initiation.

Comprised of 98 patients with MG, findings showed MG-ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively, by week 12 and the conclusion of the OLE. At week 130, the least-square mean percentage changes from baseline in MG-ADL score were –61.9% (95% CI, –69.9 to –53.9%) and –47.5% (95% CI, –59.0% to –36.0%) in early and late MG-ADL responder, respectively. By week 12 and the conclusion of the OLE, QMG response was achieved by 56.1% and 71.4% of patients, respectively.

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1. Brandsema JF, Ginsberg M, Hoshino H, et al. A phase 3, open-label, multicenter study to evaluate eculizumab in adolescents with refractory myasthenia gravis. Presented at: 2023 AAN Annual Meeting; April 22-27; in Boston, MA. Abstract 001926
2. Howard JF, Karam C, Yountz M, et al. Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses. Ann Clin Transl Neurol. 2021;8(7):1398-1407.
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