Abstract
Purpose :
Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. It is estimated that 10 million adults have diabetic retinopathy in the US alone. A substantial unmet need remains for more durable therapies for managing DR in routine clinical practice.
The Phase III GLOW Study (NTC05066230) was designed to demonstrate that tarcocimab, an anti-VEGF antibody biopolymer conjugate (ABC), is superior to sham in the treatment of non-proliferative DR (NPDR).
Methods :
Anti-VEGF treatment-naïve patients with moderately severe to severe NPDR (levels 47 and 53) were randomized 1:1 into two treatment arms: KSI-301 5 mg given on Day 1, Week 8, Week 20 and then every 24 weeks (Q24W); or sham injections at the same intervals. The primary endpoint is the change in DRSS from baseline at Week 48. Additional secondary endpoints included evaluating sight threatening complications, and the incidence of ocular and non-ocular adverse events.
Results :
A total of 253 patients were enrolled, with a mean age of 56.7 years. At baseline, 36% of patients had a DRSS Level ≤47 and 64% had a DRSS Level ≥53; mean BCVA was 81.5 letters and mean CST was 267 um. The study met its primary endpoint and the superiority in the proportion of patients with a 2-step improvement in DRSS of tarcocimab over sham was demonstrated (41.1% vs 1.4% respectively, 39.7% weighted difference, p<0.0001). In addition, all other key secondary endpoints were met with highly statistical significance, including greater reductions in the proportions of patients developing sight threatening complications (diabetic macular edema, proliferative diabetic retinopathy) vs. sham (2.3% vs 21.0%, respectively, p<0.0001). Tarcocimab was safe and well-tolerated, with similar rates of serious ocular adverse events and intraocular inflammation in both treatment groups.
Conclusions :
The adoption of approved anti-VEGF therapies for DR is constrained partly by the high treatment burden. The results from the GLOW Study demonstrate that treatment with tarcocimab in a reduced dosing regimen is superior to sham for treatment of NPDR. With a total of 4 doses in the first year and 6-month dosing, tarcocimab could represent a clinically meaningful alternative for this patient population.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.