Early Trial Data Promising for Novel DME Treatment

Dermot McGrath reports from Hamburg

Interim data from trials of a new drug for patients with advanced diabetic macular oedema (DME) shows the treatment was well tolerated, led to improvements in visual acuity, and preserved retinal structure.

Arshad M Khanani MD, MA, FASRS presented 12- and 18-week data from the BEHOLD trial, a phase 2 study of UBX1325 (UNITY Biotechnology), a novel senolytic agent for patients with advanced DME.

“The early results showed that the treatment was well tolerated with no serious adverse events and no intraocular inflammation. Patients showed improvement in best-corrected visual acuity (BCVA) through 18 weeks, and the gains were robust across a range of disease severity. The retinal structure was maintained in treated patients compared to sham-treated patients,” Dr Khanani said.

UBX1325 proposes a new mechanism of action in age-related ocular diseases by targeting Bcl-xL, a protein senescent cells rely on for survival.

“Senescent cells accumulate in areas of disease activity in both DME and wet AMD. They release mediators like growth factors, pro-fibrotic factors, as well as inflammatory factors that drive pathology. UBX1325 targets Bcl-xL to selectively drive apoptosis in senescent cells, restore vascular health, and improve vision,” he said.

The BEHOLD study is a phase 2a ongoing proof-of-concept study in previously treated patients with DME. Key inclusion criteria included patients with BCVA between 20 to 73 ETDRS letters and central subfield thickness (CST) of 300 microns or greater.

“These were previously treated patients and were required to have at least two injections in the preceding six months, with the last injection three to six weeks prior to randomisation. The mean number of injections in this patient population was four before entering this trial,” Dr Khanani said.

At baseline, patients received UBX1325 or sham and were then monitored for disease activity at every increment. For all analyses, the primary data sets included 65 patients through 12 weeks and 54 patients through 18 weeks. The study conducted BCVA and CST analyses by mixed model repeated measures (MMRM).

“We know this methodology effectively addresses the postrescue data, so the analysis presented reflects the treatment effect and is not confounded by anti-VEGF rescue injections,” Dr Khanani said.

“UBX1325 could potentially provide an important benefit as a standalone treatment.”

UBX1325 was shown as well tolerated with a favourable safety profile after a single intravitreal injection.

“Most of the ocular adverse events were associated with the injection procedure. We did not see any cases of intraocular inflammation, endophthalmitis, retinal artery occlusion, or retinal vasculitis,” he said.

In terms of efficacy, patients treated with a single injection of UBX1325 gained 6.1 ETDRS letters at 18 weeks compared to 1.1 letters for sham. The CST data was also encouraging—patients treated with UBX1325 maintained CST values compared to patients receiving sham, where CST gradually worsened over time.

Summing up, Dr Khanani said UBX1325 could potentially provide an important benefit as a standalone treatment, in combination regimen, or for use in patients who have a suboptimal response to current standard of care treatments for DME. The trial is ongoing, and UBX1325 is also under evaluation in patients with neovascular AMD in the phase 2 ENVISION study.

Dr Khanani presented the results at the 22nd EURETINA Congress in Hamburg, Germany. Arshad M Khanani MD, MA, FASRS is the Director of Clinical Research, Sierra Eye Associates, and Clinical Associate Professor at the University of Nevada, Reno, School of Medicine, US. arshad.khanani@gmail.com

Dr Khanani is a consultant for UNITY Biotechnology and receives research funding from UNITY Biotechnology.