Brolucizumab Improves Vision in Diabetic Macular Edema, Results Maintained at 100 Weeks

Brolucizumab therapy can improve visual and anatomical measures in patients with diabetic macular edema, and those results are maintained at 100 Weeks, according to phase 3 clinical trials into the treatment published in the American Journal of Ophthalmology. The visual improvements are proportionate to aflibercept and its safety profile is maintained through year 2, the investigators report.

The prospective studies randomly assigned individuals with DME-associated visual loss into 3 arms (3 mg brolucizumab, 6 mg brolucizumab [BRO3 or BRO6], or 2 mg aflibercept) in the KESTREL trial (NCT03481634); and into 2 arms (BRO6 or 2 mg aflibercept) in the KITE trial (NCT03481660). In each, participants received 5 loading doses; 6 weeks apart for brolucizumab, and monthly for aflibercept. Then, all brolucizumab groups underwent 12-week dosing (q12w), adjusted based on disease activity or stability.

From baseline to week 100, KESTREL participants receiving BRO6 improved their overall BCVA by +8.8 letters, and aflibercept +10.6. In KITE, those undergoing BRO6 advanced +10.9 letters, and with aflibercept +8.4. Fewer patients in BRO6 arms developed intraretinal or subretinal fluid compared with aflibercept. Further, of those receiving BRO6, 32.9% in KESTREL continued the q12w schedule, and 47.5% in KITE a q12w or q16w regimen.

Adverse events included the following:

• Intraocular inflammation (IOI) rate in KESTREL: 4.2% BRO6, 1.1% aflibercept
• IOI rate in KITE: 2.2% BRO6, 1.7% aflibercept
• Retinal vasculitis rate in KESTREL: 0.5% BRO6, 0% aflibercept
• Retinal vasculitis rate in KITE: 0 cases
• Retinal vascular occlusion in KESTREL: 1.6% BRO6, 0.5% aflibercept
• Retinal vascular occlusion in KITE: 0.6% both agents

“Consistent with the Year 1 findings, the 100-week results of KESTREL and KITE studies
demonstrated long-term efficacy and durability of brolucizumab in improving visual and
anatomical outcomes in patients with DME,” the investigators report. Because the safety signals previously reported also occurred in current data, “continued vigilance and monitoring for any signs of IOI-related events with prompt and intensive management is recommended.”

IOI percentages with BRO6 in the 2 trials compare similarly to HAWK (ClinicalTrials.gov Identifier: NCT02307682) and HARRIER (ClinicalTrials.gov Identifier: NCT02434328) which evaluated brolucizumab for neovascular age-related macular degeneration (nAMD).

KESTREL was conducted from July 2018 to October 2021, and KITE between July 2018 and June 2021. The studies primarily measured drug effectiveness — real-world safety data is still indicated. Another limitation of this paper is the different extension protocol of the two trials, as well as participant discontinuation rates during the height of the COVID-19 pandemic.

Disclosures: This trial was supported with funds from Novartis Pharma AG, also involved in conduct of the study. Several investigators have disclosed affiliations with Novartis and/or the biotech, medical device, or pharmaceutical industries. Please see the original reference for complete disclosures.