Tarcocimab Tedromer Shows Promise for Diabetic Retinopathy in GLOW1

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The anti-VEGF agent tarcocimab significantly improved diabetic retinopathy severity score compared with SHAM in a phase 3 study.

lead investigator Robert W. Wong, MD, from Austin Retina Associates

Robert W. Wong, MD

Credit: Austin Retina Associates

Intravitreal treatment with tarcocimab tedromer (KSI-301) resulted in a significant 41.1% 2-step or greater improvement in diabetic retinopathy severity score (DRSS) for patients with anti-VEGF naive non-proliferative diabetic retinopathy (NPDR), according to findings presented in a poster at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting.

Treatment with tarcocimab was compared with a sham injection, which saw just a 1.4% improvement in 2-step or greater DRSS. Overall, there was a 29-times increase in response rate ratio with tarcocimab (P <.0001), which was administered at up to a 6-month interval. These results successfully met the primary end point of the phase 3 GLOW1 study, resulting in a rejuvenation in interest for the medication.

"Tarcocimab given at up to 6-month dosing resulted in clinically meaningful reduction in severity of diabetic retinopathy, specifically 41% of subjects improved at least 2 steps in diabetic retinopathy severity scores compared to sham," lead investigator Robert W. Wong, MD, from Austin Retina Associates, told HCPLive over email. "We also found an 89% reduction in sight threatening complications such as advancement to proliferative diabetic retinopathy or anterior segment neovascularization when given 4 doses over twelve months as compared to sham. There was a 95% reduction of risk of developing diabetic macular edema as compared to sham."

Tarcocimab tedromer consist of an anti-VEGF antibody conjugated to a biopolymer, which is meant to extend the duration of effect for the medication by providing biologic benefits within the retina and by reducing friction. Additionally, the polymer contains other small and bioactive molecules, with a high overall drug-to-antibody ratio. "Tarcocimab is an anti-VEGF antibody biopolymer conjugate that allows for sustained treatment effect and durability as compared to current therapeutics available on the market," said Wong.

In the GLOW1 trial, the treatment was given at a progressively extended treatment interval, starting at day 1, then week 8 followed by week 20 and then every 24 weeks thereafter for a treatment-free interval of 6 months.

"As a clinician, what it is most relevant is the potential of 6-month dosing," said Wong. "The adoption of treatment has been historically limited due to the high treatment burden, so having this extended interval option can make a significant difference in the treatment of this patient."

The baseline characteristics were well matched between the groups, with a mean age across arms of 56.7 years. In the tarcocimab arm (n = 128), the mean best corrected visual acuity (BCVA) at entry was 81.8 ETDRS letters (±5.79) and in the sham group (n = 125) it was 81.2 letters (±5.76). The central subfield thickness (CST) was a mean of 268.6 (±26.3) in the tarcocimab group and 265.3 (±25.05) in the sham arm. The baseline DRSS was at 53 or greater for 64.1% of those in the tarcocimab group compared with 64.0% in the sham arm. Overall, nearly all patients completed 48 weeks on the study, at 93.8% in the tarcocimab arm and 92% in the sham group.

For the key secondary end points, tarcocimab was found to reduce the risk of developing any sight-threatening complications, with 21.0% of those in the sham group developing these complications compared with only 2.3% in the treatment arm, an 89% risk reduction (P <.0001). Diabetic macular edema occurred in 13.7% of those in the sham group compared with 0.7% in the tarcocimab arm, which was a 95% reduction in risk (P <.0001).

Overall, 70% of patients treated with tarcocimab had at least a 1-step improvement in DRSS as compared with 10% of those in the sham group. A small portion of patients (5.6%) experienced a 3-step improvement in DRSS with the anti-VEGF agent compared with none in the sham arm. Overall, there was no change in DRSS seen for 78% of those in the sham group compared with 27.3% of those in the tarcocimab arm.

Kodiak, the company developing tarcocimab tedromer, had previously paused development into the VEGF ABC, following disappointing results in studies exploring the agent for macular edema. However, findings from the GLOW1 study, which were initially presented in November 2023, resulted in the research program being restarted and dialogues between Kodiak and the FDA to commence regarding a potential pivotal study for the agent. The new development path for tarcocimab is for macular edema following retinal vein occlusion (RVO), wet age-related macular degeneration (wAMD), and NPDR, the company noted. The phase 3 GLOW2 study is currently enrolling patients with NPDR (NCT06270836).


Reference

Wong RW, Janer D, Zawadzki R, et al. Tarcocimab tedromer (KSI-301) 5mg: outcomes of the Phase 3 GLOW Study in patients with non-proliferative diabetic retinopathy. Paper presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.

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