Brolucizumab for the treatment of visual impairment due to diabetic macular edema: 52-week results from the KITE and KESTREL studies

Abstract

Purpose : Presentation of the 52-week results from KITE and KESTREL, two prospective pivotal Phase III studies evaluating the efficacy and safety of brolucizumab (BRO) versus aflibercept (AFL) for the treatment of patients with visual impairment due to diabetic macular edema (DME).

Methods : KITE (NCT03481660) and KESTREL (NCT03481634) are 2-year, ongoing, double-masked, randomized, active-controlled, multicenter studies. Adults (≥18 years of age) with type 1 or type 2 diabetes mellitus, visual impairment due to DME with a BCVA score between 78 to 23 ETDRS letters, and DME involving the center of the macula with a central subfield thickness (CSFT) ≥320µm on SD-OCT in the study eye at screening were included. In KITE, patients were randomized 1:1 to BRO 6mg or AFL 2mg; in KESTREL, the randomization was 1:1:1 to BRO 3mg, BRO 6mg and AFL 2mg. Patients in the BRO groups received 5 loading doses every 6 weeks (q6w) followed by q12w dosing in the first year, with an option to adjust to q8w at predefined disease activity assessment visits. The AFL group received 5 loading doses monthly followed by fixed q8w dosing. The primary endpoint was the change from baseline in BCVA at Week 52; secondary endpoints included the proportion of BRO patients maintained at q12w dosing up to Week 52 and the change from baseline in CST. Results from the KITE study only are included here, results from the KESTREL study (estimated primary completion, December 2020) will be available to present at congress.

Results : In KITE, the primary objective was met with BRO 6mg non-inferior to AFL 2mg in the change from baseline in BCVA at Week 52. More than 50% of BRO 6mg patients were maintained on a q12w dosing interval through Week 52, following the loading phase. BRO 6mg showed superior improvements versus AFL 2mg in the change from baseline in CST over the period of Week 40 through Week 52. BRO 6mg demonstrated an overall well-tolerated safety profile that was comparable to AFL 2mg; in addition, the rate of intraocular inflammation was equivalent between BRO 6mg and AFL 2mg.

Conclusions : Results from the KITE study show that brolucizumab offers the potential for robust vision gains and superior anatomical outcomes with q12w treatment intervals in more than 50% of patients with DME. The data from KESTREL are expected later this year.

This is a 2021 ARVO Annual Meeting abstract.