# In Silico Assessment of Limited Blood Sampling Strategies for Individualised Pharmacokinetic‐guided Dosing of Efanesoctocog Alfa in Haemophilia A Patients

## TL;DR

This study evaluates blood sampling strategies to accurately predict efanesoctocog alfa's effects in hemophilia A patients for personalized dosing.

## Contribution

Identifies effective limited sampling strategies for individualized PK-guided dosing of efanesoctocog alfa.

## Key findings

- Several LSSs met criteria for accurate prediction of PK parameters in hemophilia A patients.
- One two-sample and three three-sample strategies were suitable for prophylactic dosing.
- Six three-sample strategies met requirements for pre-operative dosing accuracy.

## Abstract

Efanesoctocog alfa is a novel factor VIII (FVIII) concentrate with a unique molecular design that enables Von Willebrand Factor‐independent clearance in patients with haemophilia A. Limited sampling strategies (LSSs) are necessary to implement accurate pharmacokinetic (PK)‐guided dosing for efanesoctocog alfa in clinical practice.

This in silico study aims to evaluate the predictive performance of 10 LSSs with one to three samples for estimating individual PK profiles of efanesoctocog alfa.

Monte Carlo simulations based on a published population PK model generated individual FVIII activity‐time profiles for a virtual population. LSSs were applied to sample from these profiles, and PK parameters, FVIII activity peak level at 0.5 h (C0.5), FVIII activity trough level at 168 h (C168) and time above FVIII activity thresholds (5, 10 and 40 IU/dL) were estimated using Bayesian forecasting.

All LSSs complied with our requirements of a relative mean prediction error of <±5% and a relative root mean square error of <25%. For prophylactic dosing advice, a LSS was considered clinically suitable if at least 80% of predicted C168 had a prediction error within −3 to 3 IU/dL. This criterion was met by one two‐sample LSS and three three‐sample LSSs. For pre‐operative dosing advice, suitability required at least 80% of predicted C0.5 within –20 to 20 IU/dL, fulfilled by one two‐sample and six three‐sample LSSs.

Several LSSs demonstrated adequate predictive performance for PK‐guided dosing of efanesoctocog alfa.