Alternative posology for brolucizumab: a 6-week loading regimen is as effective as a 4-week regimen for the treatment of nAMD.

Abstract

Background: Extending the dosing interval with the anti-vascular endothelial growth factor (VEGF) brolucizumab in the loading phase may reduce treatment burden while maintaining functional and anatomical outcomes for patients with neovascular age-related macular degeneration.

Methods: We integrated population pharmacokinetic/pharmacodynamic (PK/PD) and quantitative system pharmacology (QSP) modelling approaches to evaluate the effect of brolucizumab 6 mg on central subfield thickness (CSFT) and best-corrected visual acuity (BCVA) using an alternative reduced loading regimen (two or three administrations every 6 weeks (q6w)) followed by individualised every 12 weeks/every 8 weeks (q12w/q8w) maintenance. The simulation results were compared with the CSFT and BCVA outcomes in the phase 3 HAWK and HARRIER studies, in which patients received the approved loading regimen of 3 monthly doses.

Results: For both loading regimens, simulations of the QSP model showed almost complete VEGF inhibition during the loading phase and free VEGF recovery commenced 6‒7 weeks following the last loading dose, returning to baseline levels after 12‒13 weeks.The population PK/PD simulations showed that week 48 and week 36-48 mean BCVA and CSFT changes from baseline using the alternative loading regimen and individualised maintenance treatment were similar to HAWK and HARRIER study measures. Simulated disease activity assessments indicate that only 20% of patients needed third q6w loading dose before switching to q12w/q8w maintenance treatment.

Conclusions: This integrated modelling approach predicted that reducing the loading regimen of brolucizumab 6 mg treatment to two or three doses every 6 weeks is expected to result in similar efficacy outcomes, resulting in regulatory approval of this alternative dosing regimen in several countries.