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Ravulizumab in patients with generalised myasthenia gravis

Presented By
Dr Tuan Hoang Vu, University of South Florida Physicians Group, FL, USA
Presented by
Tuan Hoang Vu University of South Florida
AAN 2022

In the randomised, phase 3 CHAMPION MG trial, the terminal complement component 5 (C5) inhibitor ravulizumab provided rapid and sustained symptomatic improvements in patients with generalised myasthenia gravis (MG) for up to 26 weeks. These effects were sustained after 26 weeks of open-label treatment.

In most (~85%) generalised MG patients, binding auto-antibodies to the post-synaptic acetylcholine receptor (AChR) leads to activation of the complement cascade and generation of the membrane attack complex (MAC), resulting in the destruction of the post-synaptic membrane of the neuromuscular junction [1]. Treatment with a complement inhibitor led to significant improvements of symptoms in patients with refractory generalised MG [2].

The phase 3 CHAMPION MG trial (NCT03920293) enrolled 175 patients with AChR antibody-positive (AChR Ab+) generalised MG 1:1 to receive ravulizumab infusion or placebo for 26 weeks in 85 centres worldwide [3]. The experimental group received body weight-based doses of 2,400 to 3,000 mg induction on day 1, and 3,000 to 3,600 mg maintenance dose every 8 weeks starting on day 15. All participants were allowed background treatment with an acetylcholinesterase (AChE) inhibitor and an immunosuppressant. The primary efficacy endpoint was an improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL). A secondary endpoint was Quantitative Myasthenia Gravis (QMG) total score. Dr Tuan Hoang Vu (University of South Florida Physicians Group, FL, USA) presented the results.

Ravulizumab was associated with a statistically significant improvement in MG-ADL total score versus placebo (-3.1 vs -1.4; P=0.0009; see Figure). QMG total score also improved significantly compared with placebo (P<0.001), as did the proportion of patients who achieved an improvement of at least 5 points in QMG (P=0.005). Improvements in MG-ADL and QMG scores had a quick onset, within 1 week, and were maintained through week 26. No significant improvements in quality of life were detected at week 26, as measured by the Revised 15-Component Myasthenia Gravis Quality of Life score (P=0.064) or the Neuro-QOL Fatigue score (P=0.373). This result could have been influenced by the COVID-19 pandemic.

Figure: MG-ADL score improvements from week 1 through 26 [3]











*P<0.05; **P<0.01; ***P<0.001; MG-ADL, Myasthenia Gravis Activities of Daily Living; SEM, standard error of the mean.

Adverse events (AEs) were similar in both groups. The most frequently reported AEs in the ravulizumab and placebo group were headache (18.6% and 25.8%, respectively), diarrhoea (15.1% and 12.4%), and nausea (10.5% and 10.1%). Among serious AEs, the most frequent included MG crisis (ravulizumab: 1.2%) and MG worsening (placebo: 3.4%).

After completing the randomised-controlled period, participants could enter an open-label extension (OLE), during which they received ravulizumab for an additional 26 weeks [4]. After 52 weeks, treatment effects were sustained. Patients who had originally been assigned a placebo showed immediate and sustained improvements in MG-ADL and QMG scores in the OLE, which were comparable to those in the ravulizumab group during the randomised-controlled period.

  1. Howard JF. Ann N Y Acad Sci. 2018;1412(1):113–128.

  2. Howard JF, et al. Lancet Neurol. 2017;16(12):976–86.

  3. Vu TH, et al. Efficacy and safety of ravulizumab in anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: phase 3 CHAMPION MG study. Clinical Trials Plenary Session, AAN 2022, 02–07 April, Seattle, USA.

  4. Howard JF, 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: Results from the Phase 3 CHAMPION MG Open-label Extension. S25.005, AAN 2022, 02–07 April, Seattle, USA.

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