Abstract
Purpose :
OTX-TKI, an intravitreal, bioresorbable, hydrogel-based implant, is designed to deliver the small molecule tyrosine kinase inhibitor, axitinib, in a sustained-release formulation to the vitreous & can potentially address the need for a novel treatment approach for nAMD that provides a longer duration of action. Here we report the preliminary safety, tolerability & biological activity of OTX-TKI in subjects with nAMD.
Methods :
Prospective, multi-center, open-label, dose escalation Phase 1 study is ongoing. Subjects with nAMD (treatment-naïve or with a history of anti-VEGF therapy) were eligible to receive intravitreal placement of OTX-TKI. Three cohorts were evaluated: Cohort 1: 200 µg (n=6); Cohort 2: 400 µg (n=7); Cohort 3 (enrolling): 3a) 600 µg (n=5/6) & 3b) 400 µg + anti-VEGF induction therapy (n=2/6). Assessments included: Spectral-domain optical coherence tomography (SD-OCT) imaging to assess central subfield thickness (CSFT), best-corrected visual acuity (BCVA), & adverse event collection. Assessments were performed at baseline, day 0 (injection), days 3, 7, 14, & continued monthly until implants were no longer visible.
Results :
No ocular serious adverse events have been reported to date (200 µg: 9-10.5 months; 400 µg: 12+ months; 600 µg: 4.5 months; 400 µg + Anti-VEGF: 3 months ongoing follow-up). No changes in intraocular pressure were observed in any subject & no subject required steroids. CSFT was noted to remain mostly stable in the 200 µg group. In the 400 & 600 µg groups, many subjects showed a decrease in CSFT & demonstrated a clinically meaningful reduction in intraretinal &/or subretinal fluid by 2 months. Reduction was maintained for up to 13 months in one subject in the 400 µg group, while in the 600 µg group, up to 4.5 months (only subject to reach this time point so far). Implants exhibited little movement in the vitreous & were generally no longer visible after 9 - 10.5 months (200 µg).
Conclusions :
OTX-TKI appears to be generally well-tolerated to date with a favorable safety profile. Preliminary signs of biological activity, as evidenced by a decrease in CSFT in the 400 µg & 600 µg groups by two months, has been observed in many subjects with durability up to 13 months. Minimal movement & consistent resorption of implants has been observed. Study is still enrolling, and additional follow-up of current dose groups is ongoing.
This is a 2021 ARVO Annual Meeting abstract.