Abstract
Purpose :
Senescence is implicated in vascular pathology of DME. This Ph 2 study evaluated the safety and efficacy of a novel, small molecule, BCL-xL inhibitor senolytic agent and assessed the evidence of activity of a single IVT injection of UBX1325 in patients with DME previously treated with Anti-VEGF.
Methods :
This study was a prospective, randomized, double-masked trial of UBX1325 vs. sham, with follow-up of 48 weeks. 65 patients with persistent DME were randomized to receive either one IVT injection of UBX1325 10 µg or sham. The primary endpoints were safety and tolerability of UBX1325 at week 24. Secondary endpoints included BCVA and changes in BCVA, CST, changes in retinal edema, and rates of anti-VEGF rescue at weeks 24 and 48.
Results :
UBX1325 was safe and well tolerated with no intraocular inflammatory events (IOIs). 53.1% of UBX1325-treated patients did not require anti-VEGF rescue up to 48 weeks compared to only 21.9% of patients in the sham arm (p = 0.0096). UBX1325 demonstrated a sustained improvement in BCVA through 48 weeks with an increase of +6.2 ETDRS letters from baseline (p=0.0037), associated with CST stability in the subgroup of patients not requiring anti-VEGF rescue. Patients (N=7) with baseline CST >400 microns had a mean BCVA of 8.9 letters at week 48 and a decrease in CST of -39.4 microns compared to those (N=5) with baseline CST of 400 microns or less who demonstrated an increase in BCVA of 2.1 letters and 16 microns increase in CST at week 48.
Conclusions :
The study achieved Proof-of-Concept based on pre-specified criteria for the use of UBX1325 as a potential treatment for DME .
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.