Visual and expanded anatomical outcomes for brolucizumab versus aflibercept in patients with neovascular AMD: 96-week data from HAWK and HARRIER

Abstract

Purpose : To report the outcomes over 96 weeks in HAWK and HARRIER, two Phase III, prospective studies that assessed the efficacy and safety of brolucizumab (Bro) versus aflibercept (Afl) in patients with nAMD.

Methods : Patients were randomized 1:1:1 to Bro 3 mg (n=358), Bro 6 mg (n=360) or Afl 2 mg (n=360) [HAWK], or 1:1 to Bro 6 mg (n=370) or Afl 2 mg (n=369) [HARRIER]. After three monthly loading doses, Bro patients received q12w dosing with an option to adjust to q8w at predefined disease activity assessment visits; Afl was dosed in a fixed q8w regimen.

Results : In HAWK and HARRIER, Bro was non-inferior to Afl in mean BCVA change from baseline at Week 48 (primary endpoint) and the visual gains were maintained to Week 96. The mean change (±SE) in BCVA (ETDRS letters) from baseline to Week 96 in HAWK was 5.6 (0.79) for Bro 3 mg, 5.9 (0.78) for Bro 6 mg and 5.3 (0.78) for Afl and in HARRIER was 6.1 (0.73) for Bro 6 mg and 6.6 (0.73) for Afl. Bro achieved superior reductions compared with Afl in CST from baseline to Week 16 and Week 48, and these were also maintained at Week 96 (HAWK: P=0.00105 [Bro 3 mg vs Afl]; P=0.00575 [Bro 6 mg vs Afl] - Fig 1; HARRIER: P<0.0001 - Fig 2). The proportions of patients with presence of IRF and/or SRF at Week 96 in HAWK were 31% (P=0.0344), 24% (P=0.0001) for Bro 3 mg, 6 mg compared to 37% for Afl; and in HARRIER were 24% (P <0.0001) for Bro 6 mg compared to 39% for Afl. The proportions of patients with sub-RPE fluid at Week 96 in HAWK were 14% (P=0.9554), 11% (P=0.1213) for Bro 3 mg, 6 mg compared to 15% for Afl ; and in HARRIER were 17% (P=0.0371) for Bro 6 mg compared to 22% for Afl, respectively. The proportions of patients who were fluid-free (absence of SRF, IRF and sub-RPE) at Week 96 were higher for Bro 6 mg than Afl in HAWK (71.3% [Bro]; 58.8% [Afl], P=0.0006) and HARRIER (64.8% [Bro]; 52.4% [Afl], P=0.0009). These visual and anatomical outcomes were achieved with over 75% of Bro 6 mg patients who completed Week 48 on a q12w interval remaining on a q12w interval until Week 96.

Conclusions : The superior anatomic outcomes in IRF and/or SRF and CST at Week 16 and 48 along with the comparable vision gains seen with Bro 6 mg versus Afl at 48 were maintained at Week 96. Bro achieved better fluid control with more patients remaining fluid-free at Week 96 compared with Afl.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.