A recent peer-reviewed publication in the journal CPT: Pharmacometrics & Systems Pharmacology highlights how modelling and simulation (M&S) are currently used—and where important gaps remain—in the development and regulatory evaluation of CAR-T cell therapies. Developed within the ERAMET project, the study reviews European regulatory experience for CAR-T therapies approved between 2018 and 2024, with the aim of better understanding how quantitative methods can support decision-making for these complex and highly innovative treatments.
CAR-T therapies have transformed the treatment landscape for certain cancers, but their development poses significant challenges, including small patient populations, high variability, and complex manufacturing processes. These constraints make model-informed approaches particularly valuable. The analysis shows, however, that the use of modelling is uneven across domains: it is most frequently applied to pharmacokinetics, while its use for efficacy and especially safety remains limited. In addition, fewer than half of the identified regulatory questions were addressed at the time of initial approval, with many deferred to post-marketing phases, pointing to missed opportunities for earlier integration of modelling.
The study also reveals a gap between methodological advances described in the scientific literature and the more limited, less mature models used in regulatory submissions. Combined with a lack of consistency in how modelling approaches are applied and evaluated, this highlights the need for more harmonized frameworks to support their credibility and uptake. By proposing a structured way to map regulatory questions and assess modelling approaches, the publication contributes directly to ERAMET’s objective of improving transparency, consistency, and trust in model-informed drug development.
Overall, the findings underline that while M&S has clear potential to optimise dose selection, support trial design, and strengthen evidence generation, it remains underutilised in regulatory practice. Bridging this gap will be essential to accelerate the development and approval of advanced therapies such as CAR-T, ultimately improving patient access to innovative treatments.
Read the full article here.
