Phase 1 HELIOS Trial Shows Promise for OTX-TKI in Diabetic Retinopathy Treatment
Key Insights
The HELIOS Phase 1 trial demonstrated that OTX-TKI, a sustained-release axitinib formulation, significantly reduced retinal fluid and vascular leakage in patients with moderately severe to severe diabetic retinopathy (search) without center-involving diabetic macular edema (search).
OTX-TKI showed sustained therapeutic effects over the entire 12-month study period, with consistent reduction in overall retinal volume measurements and intraretinal fluid compared to sham treatment.
The treatment candidate offers potential dosing every 6 to 12 months, representing a significant reduction in treatment burden for diabetic retinopathy (search) patients.
The HELIOS Phase 1 trial has demonstrated encouraging results for OTX-TKI, a sustained-release formulation of the tyrosine kinase inhibitor axitinib, in treating diabetic retinopathy (search) without center-involving diabetic macular edema (search). The study, presented at the American Academy of Ophthalmology 2025 annual meeting and the 2025 Retina Society meeting, compared a single injection of OTX-TKI with sham treatment in patients with moderately severe to severe diabetic retinopathy.
Sustained Fluid Reduction and Vascular Benefits
Post-hoc analysis revealed that OTX-TKI treated eyes demonstrated consistent improvements in retinal fluid metrics throughout the study duration. According to Margaret A. Chang, MD, MS, who presented the findings, "OTX-TKI treated eyes compared to sham, had improvements in retinal fluid metrics for the entirety of the study. Compared to sham eyes, OTX-TKI eyes had a consistent reduction in overall retinal volume measurements over time."
The treatment showed sustained reduction in both overall retinal volume measurements and intraretinal fluid, suggesting broader effects on retinal leakage and permeability. Using spectral domain OCT, researchers found that while the sham group trended towards increased fluid, the OTX-TKI group demonstrated sustained fluid reduction throughout the study.
Vascular Leakage Analysis
Quantitative ultra-wide field angiography revealed progressive leakage in the sham group, contrasting with significant leakage reduction in the OTX-TKI group. Justis P. Ehlers, MD, noted a particularly significant finding: "The sustained leakage reduction over the entire 12-month study period, which differed from typical anti-VEGF trials where reduction is often short-lived."
The treatment demonstrated a pan-retinal effect, with consistent results across different retinal regions, indicating widespread therapeutic impact beyond localized treatment areas.
Safety Profile and Mechanism of Action
The primary goal of the Phase 1 trial was to assess safety, which showed no safety signals or signs of intraocular inflammation. OTX-TKI combines axitinib, a tyrosine kinase inhibitor, with Elutyx bioresorbable hydrogel technology for sustained drug delivery.
Chang explained the mechanism: "Axitinib is a tyrosine kinase inhibitor, works intracellularly to inhibit multiple targets. There's inhibition of all VEGF receptors, but in addition, it does not have any tie2 (search) inhibition. So remember that tie2 is the receptor for ang-one, which leads to vascular stability, so having no tie2 inhibition is a good thing."
The formulation is approximately 100 times more potent against VEGF receptor 2 (search) compared to other tyrosine kinase inhibitors, and the Elutyx polymer matrix enables controlled and sustained release of the therapeutic molecule.
Clinical Outcomes and Disease Progression
The trial results showed promising clinical outcomes, with no eyes in the OTX-TKI group developing vision-threatening complications, compared to expected progression in the sham group. This represents a significant advancement in managing early-stage diabetic eye disease, particularly given that non-proliferative diabetic retinopathy (search) currently lacks effective intervention strategies.
Ehlers emphasized the clinical significance: "Most clinicians do not use anti-VEGF therapy due to treatment burden and risk-benefit considerations, despite its potential to impact disease severity."
Future Development Plans
Two pivotal trials are planned to advance OTX-TKI development. HELIOS-2 will evaluate 12-month dosing of OTX-TKI compared to a single dose of ranibizumab 3 milligrams, while HELIOS-3 will examine either 6 or 12-month dosing compared to sham treatment.
Both studies will utilize a novel ordinal DRSS endpoint developed by Ocular Therapeutix in collaboration with the FDA. Chang noted: "This will look at both disease improvement as well as prevention of worsening, and that will hopefully allow these trials to give us a little bit more sensitive information as to how these medications are working."
Treatment Burden Reduction
The potential for dosing every 6 to 12 months represents a substantial improvement in patient quality of life through reduced treatment burden. Chang emphasized this benefit: "All together, OTX-TKI will be able to be dosed every 6 to 12 months. That's a huge gain for our patients in terms of improving their quality of life with a decrease in treatment burden."
The concept of a once-yearly treatment that could "reset the clock" on disease progression represents a paradigm shift in diabetic retinopathy (search) management, potentially offering both therapeutic benefit and practical advantages for patients and healthcare systems.