Pharmacokinetic (PK) and pharmacodynamic (PD) data for sutimlimab (Enjaymo®) support the approved dosing regimen in patients with cold agglutinin disease (CAD), without the need for further dose adjustments in specific populations, according to a study published in the Journal of Pharmacology and Experimental Therapeutics.

The approved dosing (6.5 g in patients weighing less than 75 kg, and 7.5 g in patients weighing 75 kg or more) allowed patients to attain the maximum effect of the drug, independent of covariate characteristics, and provided adequate sutimlimab exposure to maximize effects on hemoglobin (Hb), bilirubin, and total complement component C4 levels. Moreover, the results suggest that sutimlimab is well-tolerated with the approved dosing regimen.

The study’s authors observed similar changes in Hb, bilirubin, and total C4 levels from baseline following 6.5 or 7.5 g of sutimlimab and negligible changes in the placebo group. They projected a change in Hb from baseline at a steady state of 2.2 g/dL, which is consistent with observations from phase 3 study.

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To account for intersubject variability and the effects of covariates on the PK of sutimlimab and Hb, the authors developed 2 models: a population PK and a PK/PD model.

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“A dynamic population PK/PD structural model for Hb was developed by linking the complete time profile of sutimlimab concentrations to the time profiles of Hb. The PK component consisted of the final population PK model; the PD component was based on an indirect response/turnover model for Hb dynamics over time, including a zero-order rate constant (kin) for Hb production, and a first-order rate constant (kout) for elimination of Hb, which is inhibited by sutimlimab concentration in the central compartment,” the authors explained.

The PK of sutimlimab was best described by a two-compartment model with Michaelis-Menten elimination kinetics, as concluded after a comprehensive analysis of several potential structural models. This model adequately described sutimlimab PK in patients with CAD and healthy volunteers, and mirrored the nonlinearity of sutimlimab PK, which is particularly notorious at lower doses (0.3-60 mg/kg).

Body weight was identified as a covariate for the volume of distribution in the central compartment (Vc) and total body clearance of sutimlimab, and ethnicity (Japanese vs non-Japanese) was identified as covariate for Vc and maximal nonlinear clearance.

Bayesian analysis and external validation showed that the PK/PD model used in this study is suitable to describe Hb data obtained from sutimlimab studies.


Frank T, Kovar A, Strougo A, Vage C, Teuscher N, Wong N. Sutimlimab pharmacokinetics and pharmacodynamics in patients with cold agglutinin disease. J Pharmacol Exp Ther. Published online May 10, 2023. doi:10.1124/jpet.122.001511