‘Senolytic’ Therapy Shows Promise in Neovascular Eye DiseaseAugust 3, 2022
An investigational drug targeting senescent cells, UBX1325, achieved sustained improvement in visual acuity in patients with diabetic macular edema (DME) or neovascular age-related macular degeneration (AMD), according to research presented at the American Society of Retina Specialists (ASRS) meeting.
In this exclusive video, study author Raj Maturi, MD, of the Midwest Eye Institute in Indianapolis, discusses UBX1325’s mechanism of action and results of the phase I study.
The following is a transcript of his remarks:
So what is senolytic therapy? It is a specific therapy that specifically activates and kills, using caspase and apoptosis, cells that are in G0 phase or in senescence. So unlike other therapies where we try and save cells, here we are actually actively trying to kill cells. And why would this be of benefit? It’s so that other cells, the healthy cells, can reproduce and take their space. Extremely useful in wet AMD and diabetes. Some studies show that P16-positive-label cells, which is a label for senescence, happens between 10% and 15% in older populations.
So would the elimination of senescence be of help? Well in diabetes, especially in vascular disease in the mouse OIR [oxygen-induced retinopathy] model, we see that the amount of non-perfused retina — OA vascular retina — is significantly reduced by the use of UBX1325. Based on this preliminary preclinical data, the company went ahead and did a phase I single-ascending dose study using diabetics as well as AMD patients who are both treatment experienced.
In these populations, in the diabetic population first, they showed very good efficacy at 6 months with an increase in visual acuity of about 10 letters by week 2. And a lot of it which stayed all the way through week 24. In the macular-degeneration population, there was again an improvement in visual acuity very early on by week 2, with a lot of those patients not needing repeat therapy all the way through week 24 after just one dose of drug. In the AMD population, compared to the diabetic population, there was an increased need for repeat therapy.
These are phase I study data, very exciting, very positive results. It met its phase I endpoint, which is safety and no significant inflammation or other side effects in the patients. There are currently two ongoing phase II studies, one in the diabetic population and one in the AMD population with repeat dosing of UBX. I’m looking forward to seeing how this drug pans out. I’m excited that it’s a new method of therapy, and I’m excited that it has a way to decrease non perfusion.