AAO 2025: Margaret A. Chang, MD, MS, highlights OTX-TKI’s impact on retinal fluid

Margaret A. Chang, MD, MS, presented updates from the HELIOS Phase 1 trial of OTX-TKI, a sustained-release formulation of the tyrosine kinase inhibitor, axitinib, for the treatment of diabetic retinopathy (DR), at the American Academy of Ophthalmology 2025 annual meeting, held October 18-20, in Orlando, Florida. The study compared a single injection of OTX-TKI with sham in patients with moderately severe to severe DR who did not have center-involving diabetic macular edema (DME).

As Chang emphasized, “these are patients who didn't have center-involving DME,” but in clinical practice, “there are these patients who will have these little pockets of fluid outside that foveal center.” A post hoc analysis revealed that over time, eyes treated with OTX-TKI “had improvements in retinal fluid metrics for the entirety of the study.” Compared with sham, “OTX-TKI eyes had a consistent reduction in overall retinal volume measurements over time,” as well as “a consistent reduction in intraretinal fluid.”

According to Chang, these findings suggest that “OTX-TKI has more widespread effects on overall retinal leakage and permeability.” Reductions were seen across “macular fluid overall, retinal to RPE volume measurements, as well as intraretinal fluid,” and “that was really consistent for the entire study.”

She highlighted that these results point to the potential value of alternative end points: “We might want to analyze these alternative metrics, to really show how to have a better understanding of how our therapies are actually affecting the overall retina.” Moreover, “this might lead us to maybe more consistent treatment of these eyes and maybe more aggressive treatment... if we can somehow tie the retinal volume measurements to retinal function.”

Mechanistically, Chang described OTX-TKI as “basically the tyrosine kinase inhibitor, axitinib, with the Elutyx bioresorbable hydrogel technology.” Axitinib “works intracellularly to inhibit multiple targets,” notably “all VEGF receptors,” but “does not have any Tie2 inhibition.” She reminded the audience that “Tie2 is the receptor for Ang-1, which leads to vascular stability—so having no Tie2 inhibition is a good thing.” Notably, “compared to other TKIs, axitinib is about 100 times more potent against VEGF receptor 2.”

The Elutyx polymer matrix, Chang explained, “has been used in other FDA-approved indications” and enables “controlled and sustained release of the therapeutic molecule in a targeted area.” This design supports long-term dosing intervals—“OTX-TKI will be able to be dosed every 6 to 12 months—so that’s a huge gain for our patients in terms of improving their quality of life with a decrease in treatment burden.”

Looking ahead, the OTX-TKI program is advancing into pivotal trials. “Luckily, this program is going forward with two planned pivotal trials, the HELIOS-2 and the HELIOS-3 trials.” HELIOS-2 “is going to be looking at 12-month dosing of OTX-TKI,” while HELIOS-3 “is going to look at either 6 or 12-month dosing compared to sham.” Both studies will assess DR using “a new ordinal DRSS endpoint,” developed “in collaboration with the FDA.” This approach will “look at both disease improvement as well as prevention of worsening,” which Chang noted could yield “more sensitive information as to how these medications are working and hopefully lead to better and faster trial recruitment.”

Chang added that “TKIs are very, very exciting in that new space that we need for sustained delivery of better agents” not only for diabetic retinopathy, but also “DME and neovascular AMD,” ultimately aiming to “help them with quality of life and hopefully improve patient outcomes in the long term so that there aren't as many issues with lapses in care.”

REFERENCE

1. Chang MA. Macular fluid volume and retinal vascular leakage analysis following a single axitinib intravitreal hydrogel in DR. Presented at: American Academy of Ophthalmology 2025 annual meeting; October 18-20, 2025; Orlando, FL.