HAWK and HARRIER 48-week data: potential for treatment interval extension in patients with nAMD disease activity at Week 16

Abstract

Purpose : The Phase 3 HAWK (NCT02307682) and HARRIER (NCT02434328) studies evaluated the efficacy and safety of brolucizumab (Bro) versus aflibercept (Afl) in previously untreated patients with neovascular age-related macular degeneration. All patients received three monthly loading injections, then brolucizumab was injected q12w unless disease activity (DA) was identified resulting in permanent adjustment to q8w, while aflibercept was dosed q8w throughout the study, as per label at study initiation. Due to the study design, Bro patients adjusted to a q8w regimen at the end of the matched loading phase at Week 16 owing to DA could not subsequently extend to a q12w interval. The aim of this post-hoc analysis is to assess subsequent DA in patients with DA at Week 16 to determine the potential for interval extensions during the first year of treatment if the protocol had allowed it.

Methods : In Year 1 of HAWK and HARRIER, disease activity assessments (DAA) were conducted at Weeks 16, 20, 32, and 44 in both studies for all Bro and Afl patients regardless of whether DA was detected at earlier visits or not; presence of DA was determined at the discretion of the masked investigator. This post-hoc analysis evaluated the absence of DA, and thus potential for interval extension, in the matched cohort of Bro and Afl patients with DA at Week 16 using pooled data from the Bro 6 mg arms and Afl arms of both studies. Absence of DA at two consecutive DAA was considered a surrogate for stable disease control.

Results : At the first DAA at Week 16, more Bro vs Afl patients had no DA (77.0% [n=540/701] vs 67.5% [n=470/696]). Within the subgroup of patients with DA at Week 16, more Bro than Afl patients had absence of DA at each subsequent DAA in Year 1 (Fig 1). Furthermore, a higher proportion of Bro vs Afl patients had DA absence at two consecutive DAA (Week 20/32: Bro=56.8%, Afl=45.2%; Week 32/44: Bro=66.9%, Afl=51.2%).

Conclusions : Conclusions: In HAWK and HARRIER, more Bro- vs Afl-treated patients with DA at Week 16 had no DA at subsequent assessments from as early as Week 20, including at consecutive DAAs. These findings indicated a higher potential for treatment interval extension and robust and stable disease control with Bro within the first year of treatment.

This is a 2021 ARVO Annual Meeting abstract.