Ophthalmology, January 2020
In two similarly designed phase 3 trials (HAWK and HARRIER), Dugel et al. compared the efficacy and safety of brolucizumab and aflibercept for treatment of neovascular age-related macular degeneration. The findings of both studies indicate that brolucizumab is noninferior to aflibercept in terms of visual function at week 48. Anatomic outcomes were better with brolucizumab, and overall safety was comparable for the two treatments.
Both studies were double-masked, active-controlled trials, with a combined enrollment of 1,817 patients. All patients had untreated active choroidal neovascularization caused by age-related macular degeneration (AMD) in the study eye.
Participants were assigned randomly to receive intravitreal brolucizumab (3 mg or 6 mg) or aflibercept (2 mg). After three monthly injections (loading dosage), brolucizumab-treated eyes received an injection every 12 weeks (q12w), which was adjusted to every eight weeks (q8w) if disease activity persisted. Aflibercept-treated eyes received q8w dosing.
The primary hypothesis of the study was noninferiority of brolucizumab in best-corrected visual acuity (BCVA) mean change from baseline to week 48 (margin: 4 letters). Other key end points were the anatomic outcomes and the proportion of patients who maintained q12w dosing of brolucizumab through week 48.
Forty-eight weeks after treatment was begun, each arm of brolucizumab showed noninferiority to aflibercept in BCVA change from baseline: least squares (LS) mean in the HAWK study was +6.6 (6 mg) and +6.1 (3 mg) letters with brolucizumab versus +6.8 letters with aflibercept. In the HARRIER study, LS mean values were +6.9 letters for brolucizumab (6 mg) versus +7.6 letters for aflibercept. The p value was <.001 for all comparisons of brolucizumab and aflibercept. More than 50% of eyes treated with 6 mg of brolucizumab were maintained on q12w dosing through week 48 (56% in HAWK, 51% in HARRIER).
At week 16, before any variations in treatment exposure, disease activity was more common with aflibercept than with brolucizumab 6 mg (HAWK: 34.5% vs. 24.0%, p = .001; HARRIER: 32.2% vs. 22.7% p = .002). Reductions in central subfield thickness from baseline to week 48 were greater with brolucizumab 6 mg than with aflibercept in HAWK (LS mean, –172.8 μm vs. –143.7 μm; p = .001) and in HARRIER (LS mean, –193.8 μm vs. –143.9 μm; p < .001). Anatomic retinal fluid outcomes favored brolucizumab. Overall, adverse event rates were similar for the study drugs.
The authors noted that the forthcoming 96-week data will provide further insight into the efficacy and safety of brolucizumab (q12w and q8w) relative to aflibercept (q8w).
The original article can be found here.