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

AIM: Paroxysmal 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. METHODS: We 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. RESULTS: Maintenance-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. CONCLUSION: Individualized 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.