Diabetics tend to develop retinopathy and macular edema, disrupting retinal structure and function, and leading to progressive and presently irreversible blindness. The presence of senescent cells is likely a significant contribution to this process, the retina negatively affected by the pro-inflammation, pro-growth signals produced by these errant cells. UNITY Biotechnology, one of the earliest biotech companies working on senolytics to clear senescent cells, has been pursuing the strategy of local administration of small molecule senolytic drugs, using low doses to only destroy senescent cells in one area of the body. This is an approach that failed for osteoarthritis in the knee, but appears to be working for macular edema in the eye. Local administration of senolytics in human clinical trials is an expensive way to test whether or not the impact of the inflammatory signaling of senescent cells is localized to a meaningful degree, a topic on which there is some debate, and in which the answers may differ considerably from tissue to tissue.
UNITY Biotechnology, a biotechnology company developing therapeutics to slow, halt, or reverse diseases of aging, today announced 12-week and 18-week data from its Phase 2 BEHOLD study of UBX1325, a senolytic Bcl-xL inhibitor, in patients with diabetic macular edema (DME).
At 18 weeks after a single UBX1325 injection, the mean change in best corrected visual acuity (BCVA) of UBX1325-treated subjects was an increase of 6.1 ETDRS letters, representing an improvement of +5.0 ETDRS letters compared to sham-treated subjects. In addition, patients treated with UBX1325 maintained central subfield thickness (CST) compared to sham-treated patients who demonstrated progressive worsening of CST (i.e., increased retinal thickness) through 18 weeks. The separation of UBX1325-treated patients from sham-treated patients at 18 weeks in measures of both visual function and retinal structure following a single UBX1325 injection suggests that one dose could have a durable therapeutic effect. The current standard of care for DME with the leading anti-VEGF therapeutic requires 3-5 monthly loading doses followed by every 8-week dosing, imposing a significant treatment burden on patients.
"The 12- and 18-week results are especially impressive considering that UBX1325 was given as a single injection in a patient population in which anti-VEGF treatment was no longer providing optimal benefit. The vision gains observed are greater than what has been previously reported with the standard of care in similar patient populations, and the durability of effect suggests that UBX1325 could address the large unmet need for longer-lasting, disease-modifying treatments for patients with DME. These data represent an important and exciting step in validating the senolytic therapeutic concept that is core to UNITY's platform."