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  • Brolucizumab Holds Promise for DME

    By Lynda Seminara
    Selected by Richard K. Parrish II, MD
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    Journal Highlights

    American Journal of Ophthalmology, June 2022

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    Brolucizumab, a single-chain antibody fragment that offers deep tissue penetra­tion and a long duration of action, has gained interest as a possible treatment option that may be more patient-friend­ly than traditional regimens for diabetic macular edema (DME). According to work by Brown et al., the 52-week results of two phase 3 randomized trials suggest that the visual gains from brolucizumab 6 mg are noninferior to those of aflibercept 2 mg and that the newer drug is better at reducing central subfield thickness (CST) and resolving retinal fluid. Brolucizumab showed a favorable risk/benefit profile, and more than 50% of patients maintained their 12-week dosing schedule.

    The two double-masked multi­national trials (KESTREL and KITE) included patients with type 1 or 2 dia­betes whose hemoglobin A1c level was ≤10%; their BCVA letter score ranged from 23 to 78. In KESTREL, participants (N = 566) were assigned randomly (1:1:1) to receive brolucizumab 3 mg, brolucizumab 6 mg, or aflibercept 2 mg. In KITE (N = 360), the randomization (1:1) was to brolucizumab 6 mg or aflibercept 2 mg. Baseline demograph­ics were similar for all cohorts.

    Patients who received brolucizumab started with five loading doses every six weeks, followed by dosing every 12 weeks (q12w) with the option to adjust or stop dosing at eight-week intervals if disease activity was observed. Patients treated with aflibercept initially received five doses every four weeks (loading period), followed by fixed dosing at eight-week intervals. The main outcome for both trials was BCVA change from baseline to week 52. Only one eye per patient was entered into the analyses.

    At week 52, brolucizumab 6 mg demonstrated noninferiority to aflibercept. The mean BCVA gains from baseline, respectively, were 9.2 versus 10.5 letters in KESTREL and 10.6 versus 9.4 letters in KITE (p < .001). In both studies, the percentage of patients with CST <280 mm was higher with brolucizumab at weeks 32 and 52. Persistent subretinal and/or intraretinal fluid at week 52 was less common with brolucizumab.

    The percentage of patients on brolucizumab 6 mg who maintained the q12w dosing regimen through 52 weeks was 55.1% in KESTREL and 50.3% in KITE. In KESTREL, the rate of serious ocular adverse events was 3.7% and 1.1% with brolucizumab 3 mg and 6 mg, respectively, and 2.1% with aflibercept. In KITE, the incidence of such events was 2.2% with brolucizumab 6 mg and 1.7% with aflibercept.

    Based on these findings, brolucizumab may be an effective DME treatment that can reduce burdens for patients, clinicians, and health care systems, said the authors. They noted that 100-week data are forthcoming and should provide more insight into the drug’s safety and efficacy.

    The original article can be found here.