Efficacy, durability and safety of KSI-301 antibody biopolymer conjugate in wet AMD – Year 1 primary endpoint results from the pivotal DAZZLE study

Abstract

Purpose : Reducing the treatment burden currently required for optimal management of high-prevalence retinal exudative and vascular diseases is a key focus of next-generation therapeutics development. KSI-301 is an antibody biopolymer conjugate designed to provide potent and long-lasting intraocular vascular endothelial growth factor (VEGF) suppression. Early clinical studies in treatment-naïve patients showed strong efficacy with clinical durability of up to 6-months in patients with wet age-related macular degeneration (wAMD) with an encouraging safety profile. The objective of the pivotal DAZZLE study is to demonstrate that KSI-301 is non-inferior to aflibercept while providing a clinically meaningful reduction in intravitreal injection burden.

Methods : In this prospective, double-masked, multicenter, pivotal clinical trial, treatment-naïve patients with wAMD were randomized 1:1 into two treatment arms: KSI-301 (5 mg) or aflibercept (2 mg). Each subject was scheduled to receive three monthly loading doses of their assigned treatment. Thereafter, subjects in the aflibercept arm continued on every-other-month dosing. The dosing regimen for the KSI-301 treatment arm was every 3 to 5 months based on protocol-specified disease activity assessments. The primary efficacy endpoint was the mean change from baseline in best corrected visual acuity (BCVA) at Year 1 (Figure 1).

Results : 557 subjects across 69 sites in the United States and Europe were randomized and received study treatment. The mean age at randomization was 76.4 years and 62.1% were female. At baseline, mean BCVA was 63.6 ETDRS letters with 44% of patients having a Snellen equivalent of 20/40 or better; mean baseline central subfield thickness (CST) was 354.9 um. The primary efficacy, durability and safety results of this pivotal clinical study will be presented for the first time at the meeting.

Conclusions : Treatment outcomes with currently available anti-VEGF therapies are dependent on a treatment frequency that is challenging to sustain or inaccessible in real-world clinical settings. The DAZZLE study’s efficacy, durability and safety results will provide important confirmatory evidence on the potential role for KSI-301 as a more durable anti-VEGF treatment option for patients with wet AMD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1. DAZZLE Study (NCT04049266) Schematic design.