Kodiak Sciences Inc. (NASDAQ:KOD), a precommercial retina-focused biotechnology company committed to researching, developing and commercializing transformative therapeutics, today announced positive topline results in the GLOW2 Phase 3 superiority study of Zenkuda™ for the treatment of patients with diabetic retinopathy. Zenkuda (tarcocimab tedromer) is an anti-vascular endothelial growth factor (VEGF) intravitreal biologic built on Kodiak's proprietary antibody biopolymer conjugate (ABC®) platform.

 

GLOW2 is a confirmatory Phase 3 study designed to replicate and extend the findings of the positive pivotal GLOW1 study, in which Zenkuda demonstrated superiority versus sham in the treatment of patients with moderately severe and severe diabetic retinopathy (DR). GLOW2 expanded the population to include patients with proliferative diabetic retinopathy (PDR) and mild diabetic macular edema (DME), alongside patients with moderately severe to severe diabetic retinopathy. Baseline characteristics were well-matched between groups and were typical of treatment-naïve diabetic retinopathy patients. See Figure 1.

In GLOW2, patients were randomized to receive either sham injection or Zenkuda via intravitreal injection at progressively extended intervals after a loading phase, with all patients on 6-month dosing by the end of the study (dosing at baseline, Week 4, Week 8, Week 20 and Week 44). A total of 62.5% of patients treated with Zenkuda achieved a ≥2-step improvement in DRSS score at Week 48, compared with 3.3% in the sham group, meeting the primary endpoint of superiority to sham with high statistical significance (p<0.0001). See Figure 2.

Zenkuda also demonstrated superiority in the two alpha-controlled secondary endpoints, with high statistical significance:

  • Zenkuda demonstrated superiority in the key secondary endpoint of reducing the risk of developing prespecified sight-threatening complications, including new or worsening proliferative DR or center-involving DME, by 85% compared to sham through Week 48 (2.4% with Zenkuda versus 15.8% with sham, p=0.0001). These results support the GLOW1 study results, in which Zenkuda reduced this risk by 89%. See Figure 3



     
  • 13.7% of patients on Zenkuda achieved a ≥3-step improvement in DRSS versus 0% with sham (p<0.0001), an improvement comparable to GLOW1, in which 5.6% of patients on Zenkuda achieved a ≥3-step improvement in DRSS versus 0% with sham. See Figure 4

Zenkuda was well-tolerated with low rates of common ocular adverse events. Notably, no cases of intraocular inflammation were reported in the study, and no cases of retinal vasculitis or occlusive retinal vasculitis were observed. The incidence of cataract in the study eye was low (2.3% with Zenkuda versus 1.6% with sham) and in line with expected background rates in patients with DR. See Figure 5.

Consistent with a real-world diabetic patient population, GLOW2 included patients using GLP-1 medications. These patients were well-balanced between treatment arms (GLP-1 use was 46.1% in the Zenkuda arm and 42.4% in the sham arm). Among patients using GLP-1 medications, Zenkuda achieved a ≥2-step improvement in DRSS from baseline to Week 48 in 60.0% of patients compared with 64.3% in patients not using GLP-1 medications.