Angiogenesis 2022 – Intravitreal Hydrogel-Based Axitinib Implant (OTX-TKI) for the Treatment of Neovascular AMD: Phase I Trial Data

Avni P. Finn MD, MBA
Assistant Professor of Ophthalmology
Vanderbilt Eye Institute, Nashville, TN

Dr. Andrew Moshfeghi from the University of Southern California Roski Eye Institute presented an update on the Phase I trial data for OTX-TKI. This therapeutic, designed to treat neovascular AMD, combines a novel mechanism of action with a mode of delivery that allows for increased durability. Axitinib is a small molecule multi-receptor tyrosine kinase inhibitor, which has the potential to be a broad anti-angiogenic through the inhibition of VEGF receptor-1,2,3 and PDGF receptor signaling. The molecule is delivered via a polyethylene glycol-based hydrogel that completely biodegrades over time in the vitreous with the goal of delivering Axitinib over 6 to 9 months.

This Phase I trial enrolled 23 subjects in four dose escalating cohorts, with the fourth cohort also receiving anti-VEGF. The results of the trial showed the Axitinib implant was well-tolerated with no serious ocular events occurring in the four cohorts. In the lower dose cohorts, retinal fluid was noted to decrease around 2 months, and in the higher dose cohort, which was combined with anti-VEGF, fluid decreased as early as one week. This early data is promising as over 60% of patients enrolled in the trial demonstrated durability of 6 months or longer, and this was as high as 80% in the higher dose cohort.

OTX-TKI is currently being evaluated in an ongoing Phase 1b, US-based multicenter trial. In this trial of the patients enrolled will receive anti-VEGF induction along with the Axitinib implant. This is a potentially promising new therapeutic for patients with neovascular AMD given the combination of a novel mechanism with longer duration of action.