Andrew Chang1,2, James Warburton4, Andreas Weichselberger5, Peter Sallstig6
Purpose: Brolucizumab is an anti-vascular endothelial growth factor antibody fragment evaluated for the treatment of neovascular age-related macular degeneration (nAMD). Results from 2 previous Phase I/II studies support that brolucizumab has potentially greater duration of effect compared with existing anti-VEGF treatments, and provided the basis for the ongoing Phase III studies.
Methods: HAWK and HARRIER (NCT02307682 and NCT02434328) are 2-year, randomized, double-masked, multicenter studies comparing the efficacy and safety of brolucizumab vs aflibercept in nAMD subjects. Based on analyses from previous studies, HAWK and HARRIER assess an alternative to ‘treat and extend’ regimen, subjects in the brolucizumab arm who meet prespecified criteria will be treated on a q12-week interval after the loading phase with the option for a q8-week interval in case of disease activity.
Results: Primary efficacy endpoint is change in best-corrected visual acuity (BCVA) from baseline to Week 48. Key secondary endpoints include average change in BCVA from baseline for Weeks 36-48 and q12-week treatment status at Week 48. Following the loading phase of 3 4-week injections, brolucizumab subjects will be evaluated twice for disease activity in the first ‘learning’ q12-week cycle and once after at the end of each subsequent q12-week cycle. If disease activity is identified, subjects will be reassigned to receive q8-week injections thereafter, up to study exit.
Conclusions: The alternative treatment regimen of HAWK and HARRIER allows evaluation of the potential of brolucizumab for q12-week dosing. Brolucizumab may potentially address an unmet clinical need in the treatment of nAMD patients by reducing treatment burden.
COMPARISON OF RANIBIZUMAB AND AFLIBERCEPT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED FOLLOWING A ?TREAT AND EXTEND? PROTOCOL: EFFICACY VARIABLES FROM THE PRE-SPECIFIED 12- MONTH INTERIM ANALYSIS OF THE RIVAL STUDY