Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency.

aimParoxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired haematopoietic stem cell disorder. Crovalimab, a complement C5-inhibitor, is approved for PNH and can be self-administered subcutaneously every 4 weeks, offering a more convenient route than intravenous C5-inhibitors. Since exposure often exceeds pharmacokinetic targets and varies with body weight, we aimed to explored individualized dosing of crovalimab using clinical trial simulations to optimize therapy.

methodsWe compared standard, weight-based and therapeutic drug monitoring (TDM)-guided regimens in treatment-naïve PNH patients over 52 weeks by means of clinical trial simulations based on the population pharmacokinetic model developed by the market authorization holder.

resultsMaintenance-phase crovalimab concentrations were generally supratherapeutic with substantial variability. Weight-based dosing reduced this variability, while TDM-guided dosing further minimized it and allowed dose intervals to be prolonged in 24% of patients to a mean of 5.0 weeks, while maintaining exposure comparable to the standard regimen.

conclusionIndividualized dosing of crovalimab may reduce exposure variability and enable less frequent dosing, supporting the feasibility of more flexible cost-effective and patient-tailored treatment regimens.