Discussion
ravulizumab
The RCP of the CHAMPION MG phase 3 trial demonstrated the efficacy and well-tolerated profile of ravulizumab administered every 8 weeks in adult patients with AChR Ab+ gMG [For many of the treatments used in patients with AChR Ab+ gMG, there are limited data on the speed of onset of effect. The present analysis of data from the CHAMPION MG study shows that ravulizumab weight-based dosing in patients with AChR Ab+ gMG achieves target serum concentrations immediately after the first dose (within 30 min of the end of infusion). Furthermore, these concentrations were sustained, irrespective of patient body weight (ranging from 40 to 166 kg), through 26 weeks of treatment (maintenance dose administered every 8 weeks). The weight-based dosing regimen reduced exposure differences across the adult body weight range. The pharmacokinetic findings are consistent with ravulizumab’s mean elimination half-life of 56.6 days (8.1 weeks) [The pharmacodynamic analyses presented here support ravulizumab’s mechanism of action, demonstrating that it rapidly blocks serum free C5, achieving complete inhibition of terminal complement (serum free C5 < 0.5 μg/mL) by the end of the initial infusion and sustaining this inhibition through the 26-week treatment period. In a previous pharmacodynamic analysis, eculizumab achieved complete inhibition of terminal complement at all time points in 92% of patients with gMG treated with the drug in a clinical study [PLEX/PP and IVIg have been shown to reduce serum ravulizumab concentrations and a supplemental dose of ravulizumab is required to compensate for these interventions [These pharmacokinetic and pharmacodynamic findings—rapid achievement of therapeutic ravulizumab concentrations and rapid inhibition of serum free C5 concentrations that were sustained through the 26-week treatment period—support the clinical results of the CHAMPION MG study, which showed the treatment effect of ravulizumab appeared within the first week following infusion and was sustained throughout 26 weeks [It is interesting to speculate why the clinical response to complement inhibition is so rapid, given that complement activation putatively destroys the NMJ postsynaptic AChR and/or membrane [Overall, ravulizumab appears well placed to offer a sustained treatment effect, without the burdensome side effects associated with long-term immunosuppressive therapies [