Eculizumab's Myasthenia Gravis Benefits Sustained in Long-Term Extension Study


Eculizumab showed sustained activity and tolerability through 3 years for generalized myasthenia gravis.

Dr Srikanth Muppidi

Srikanth Muppidi, MD, clinical associate professor, Neurology & Neurological Sciences, Stanford Medicine

Srikanth Muppidi, MD

Treatment with eculizumab (Soliris) continued to show sustained activity and tolerability through 3 years of follow-up for patients with anti-acetylcholine receptor (AChR) antibody—positive generalized myasthenia gravis (gMG), according to a presentation at the 2018 AANEM Annual Meeting.1

Findings for the long-term follow-up presented at the AANEM meeting were from an open-label extension of the pivotal phase 3 REGAIN study in which patients in the placebo arm had crossed over to receive eculizumab while those in the investigational arm continued the immunosuppressive drug. Overall, patients in the initial placebo group achieved the same level of improvement in activities of daily living (ADL), muscle strength, and functional ability as those initially randomized to eculizumab. For both arms, improvement was seen quickly following treatment and remained consistent throughout the 3-year assessment.

Based on findings from the REGAIN study, in October 2017, eculizumab was approved by the FDA as a treatment for patients with anti-AchR antibody—positive gMG. This approval marked the first in nearly 60 years for the disorder. Eculizumab is also approved to treat paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

"These results demonstrate the long-term benefits of eculizumab in previously difficult-!o-treat patients, and they support sustained effectiveness and tolerability," said presenter Srikanth Muppidi, MD, clinical associate professor, Neurology & Neurological Sciences, Stanford Medicine. "During REGAIN and the open-label study, patients treated with eculizumab experienced rapid improvements in ADL, muscle strength, functional abilities, and quality of life."

The RAGAIN trial randomized 125 patients to receive eculizumab (n = 62) or placebo (n = 63). Of these patients, 117 entered the open-label extension study: 56 from the eculizumab arm and 61 from the placebo group. At the time of the data-cutoff for the analysis, there were 42 patients remaining in the initial eculizumab arm and 43 of those from the placebo group. In both groups, the most common cause of discontinuation was patient or physician withdrawal.

The mean age of those enrolled in the open-label study was 47.4 years, and 67.5% were female. Most patients were Caucasian and had an MG disease duration of more than 10 years. Prior to entering the study, almost all patients had received 2 or more immunosuppressive treatments (98%), with half (52%) receiving 3 or more.

In the REGAIN study,2 sensitivity analyses for MG-ADL showed a significant improvement with eculizumab over placebo (-4.2 vs -2.3, respectively; P = .0058) and for quantitative MG score (-1.6 vs -4.6, for placebo and eculizumab, respectively; P = .0006). Improvements were also seen in MG composite scale (-4.8 vs -8.1, respectively) and 15-item MG quality of life (-5.4 vs -12.6, respectively).

In the open-label extension, those receiving eculizumab in the initial placebo arm enjoyed a similar magnitude of benefit as patients initially randomized to the investigational arm. This level of benefit was sustained throughout the analysis.

At the end of the REGAIN study, 25% those in the eculizumab arm had minimal manifestations by MG Foundation of America post-intervention status, as compared with 14% in the placebo group. Of those measurable at week 130 in the open-label extension, 69% had minimal manifestations in the initial eculizumab arm (n = 13) as did 53% of those who switched from placebo to the active agent (n = 15).

Overall, those in the open-label study experienced a 74% drop in the rate of exacerbation compared with 1 year prior to the start of the REGAIN study (P < .0001). Exacerbations dropped by 65% with eculizumab in the open-label arm compared with the placebo group of REGAIN (P = .0057).

MG-related hospitalization dropped by 83% and 71% with eculizumab in the open-label study compared with pre-study and the placebo group of REGAIN, respectively. There was also a 66% reduction in the use of rescue therapy in the open-label study compared with the placebo group of REGAIN (P = .0072).

During the open-label study the most common adverse events were headache (37.6%), nasopharyngitis (31.6%), diarrhea (23.1%), and upper respiratory tract infection (23.1%). The most common serious adverse event was worsening of MG (12.8% of patients). There were no cases of meningococcal infection.

"The tong-term safety profile of eculizumab in gMG is consistent with its known safety profile from over 10 years of clinical use in other indications," said Muppidi.

In addition to its approved indications, eculizumab is also being explored as a treatment for relapsing neuromyelitis optica spectrum disorder (NMOSD). In September 2018, Alexion, the company developing the drug, announced that eculizumab successfully reduced the risk of adjudicated on-trial relapsed by 94.2% versus placebo in the phase 3 PREVENT trial for NMOSD. The company noted that detailed results from the study would be presented at a future medical meeting.


  1. Muppidi S, O'Brien F, Wang J-J, et al. Long-Term Effectiveness and Safety of Eculizumab in Generalized MG: Beyond MG-ADL and QMG. Presented at: 2018 AANEM Annual Meeting, National Harbor, MD, October 10-13, 2018.
  2. Howard JF, Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16:976-986.
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