Brolucizumab 6mg 6-week loading regimen matches 4-week efficacy for nAMD, reducing treatment burden

Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss, traditionally managed with frequent intravitreal anti-VEGF injections. While anti-VEGF therapies like brolucizumab have revolutionized treatment by blocking VEGF activity and abnormal blood vessel growth, the high treatment burden of frequent injections, especially during the initial loading phase, often leads to patient non-compliance. Extending the dosing interval of potent anti-VEGF agents could significantly improve patient quality of life and adherence, addressing a critical gap in current nAMD management.

Researchers employed integrated population pharmacokinetic/pharmacodynamic (PK/PD) and quantitative system pharmacology (QSP) modeling to evaluate an alternative brolucizumab loading regimen. The study simulated the effect of brolucizumab 6 mg administered as two or three doses every 6 weeks (q6w), followed by individualized q12w/q8w maintenance. Primary endpoints were changes in central subfield thickness (CSFT) and best-corrected visual acuity (BCVA). These simulated outcomes were then compared against the established results from the phase 3 HAWK and HARRIER clinical trials, which used the approved 3 monthly dose loading regimen.

The QSP model simulations demonstrated almost complete VEGF inhibition during both the standard and alternative loading phases. Free VEGF recovery commenced 6–7 weeks following the last loading dose, returning to baseline levels after 12–13 weeks. The PK/PD simulations indicated that mean BCVA and CSFT changes from baseline at week 48 and weeks 36-48 using the alternative q6w loading regimen and individualized maintenance were similar to those observed in the HAWK and HARRIER studies. Simulated disease activity assessments further suggested that:

Only 20% of patients would require a third q6w loading dose before transitioning to q12w/q8w maintenance treatment. This modeling approach predicted comparable efficacy outcomes despite a reduced injection frequency during the loading phase.