Phase III studies of brolucizumab versus aflibercept in nAMD: 48-week primary and key secondary outcomes from HAWK/HARRIER

Abstract

Purpose : Brolucizumab is a single-chain antibody fragment with potent anti-VEGF attributes. Its molecular structure enables concentrated molar dosing and may facilitate effective tissue penetration, which together may support a long-lasting effect. This study compared the efficacy and safety of brolucizumab versus aflibercept.

Methods : Patients were randomized 1:1:1 to brolucizumab 3mg (n=358), 6mg (n=360) or aflibercept 2mg (n=360) (HAWK), or 1:1 with either brolucizumab 6mg (n=370) or aflibercept 2mg (n=369) (HARRIER), given as intravitreal injections. One eye of each patient was designated as the study eye. After three loading doses, brolucizumab patients were treated every 12 weeks (q12w), with the possibility of adjusting to 8-week dosing (q8) during the first q12 interval and at each scheduled q12 treatment visit (fig.1); aflibercept patients were treated on a q8w interval, as per label. The primary endpoint was non-inferiority of brolucizumab to aflibercept in best corrected visual acuity (BCVA) change from baseline at Week 48 (4 letter margin). Key secondary endpoints were average change in BCVA from baseline over weeks 36-48, proportion of patients on q12 treatment interval at Week 48 and change in anatomical and safety parameters.

Results : For the brolucizumab 6mg arm, 57% and 52% of patients, in HAWK and HARRIER respectively, were maintained on a q12w interval up to Week 48. Mean change in BCVA from baseline to Week 48 for brolucizumab was non-inferior versus aflibercept in both studies (p<0.0001, both studies). At Week 48 in HAWK, mean change in BCVA (±SE) for brolucizumab 3mg, brolucizumab 6mg and aflibercept 2mg was 6.1 (0.69), 6.6 (0.71) and 6.8 (0.71) ETDRS letters, respectively. At Week 48 in HARRIER, mean change in BCVA (±SE) for brolucizumab 6mg and aflibercept 2mg was 6.9 (0.61) and 7.6 (0.61) letters, respectively. Average change in BCVA over weeks 36-48 was also non-inferior (p<0.0001, both studies). Reductions in central subfield thickness were greater, and significantly fewer patients had IRF and/or SRF in the brolucizumab 6mg group versus aflibercept. Overall, safety signals were comparable between treatment arms.

Conclusions : Brolucizumab met the primary endpoint of non-inferiority in BCVA change versus aflibercept, with the majority of brolucizumab patients maintained on a q12w dosing regimen after loading until Week 48.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Fig 1: Treatment regimens