CONFERENCE UPDATE: AAN 2024

Final results from CHAMPION MG OLE demonstrated the long-term efficacy and safety of ravulizumab in adults with AChRAb+ gMG

NEUROLOGY
05 Jul 2024

STUDY DESIGN

Autoantibodies against the acetylcholine receptor (AChR) are often found in patients with generalized myasthenia gravis (gMG), which destroy the post-synaptic membrane of the neuromuscular junction (NMJ) via aberrant complement cascade activation.1 Humanized monoclonal antibodies with a high affinity to the human terminal complement component C5 such as ravulizumab inhibit the membrane attack complex formation.1 Previously, the 26-week randomized controlled period (RCP) of the phase 3 CHAMPION MG study demonstrated the efficacy and safety profile of ravulizumab in adult patients with anti-acetylcholine receptor antibody-positive (AChRAb+) gMG.1

To evaluate the long-term efficacy and safety of ravulizumab in the indication, patients were also invited to enter the open-label extension (OLE) phase.1 Those who entered OLE (n=161) were given intravenous (IV) ravulizumab on a weight-based loading dose on day 1, proceeded to receive a weight-based maintenance dose on day 15, then every 8 weeks for up to 4 years.1 This analysis included data from these patients for up to 164 weeks (RCP: 26 weeks; OLE: 138 weeks).

Changes in patient-reported Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score and physician-assessed Quantitative Myasthenia Gravis (QMG) total score from RCP and OLE baseline were assessed which were analyzed using a mixed-effect model for repeated measures (MMRM).1 Other endpoints included MG-ADL response rate, minimal symptom expression (MSE), corticosteroid (CS) use, as evaluated by changes in CS dose and proportion of CS treatment discontinuation.1 The safety and tolerability of ravulizumab were also assessed.1

FINDINGS

Efficacy endpoints:
  • The efficacy endpoints included changes from the OLE baseline in the MG-ADL total score, QMG total score, MG-ADL response rate, MSE and CS use1
  • Patients who received ravulizumab throughout the study had improvements in the MF-ADL total score (LS mean change: -4.0 [95% CI: -5.3 to -2.8]; p<0.0001) and QMG score (LS mean change: -4.3 [95% CI: -6.0 to -2.7]; p<0.0001) over 164 weeks1
  • Patients who were switched from placebo in RCP showed rapid improvement in MG-ADL score from OLE baseline and remained consistent over 138 weeks (LS mean change: -2.1 [95% CI: -3.3 to -0.9]; p=0.0005) and QMG score (LS mean change: -3.0 [95% Cl: -4.6 to -1.4]; p=0.0003)1
  • 88% of patients assessed for response to ravulizumab achieved ≥2 points improvement in MG-ADL total score and 42% of responders achieved MSE (i.e. MGA-ADL total score of 0 or 1)1
  • A decrease in concomitant CS dosage with 12% of patients stopping CS treatment by the last assessment was associated with ravulizumab treatment1

Safety:
  • The overall safety findings were consistent with the known safety profiles of ravulizumab and complement inhibitors1
  • Although 96.4% of participants experienced at least 1 AE, 40.8% were related to ravulizumab and 87.0% were of grade 1 severity1
  • The most frequently reported AEs were coronavirus disease 2019 (COVID-19) (36.1%), headache (23.1%), diarrhea (17.2%), arthralgia (13.6%) and nausea (13.0%)1

 

“Overall, these findings support the sustained clinical effectiveness and long-term safety of ravulizumab, administered every 8 weeks, in adults in AChRAb+ gMG” 

Dr. Tuan Vu
University of South Florida Morsani College of Medicine,
Florida, United States

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