UNITY Biotechnology announces results from Phase 2 BEHOLD study of patients with DME

A single injection of UBX1325 led to a statistically significant and clinically meaningful improvement in Best Corrected Visual Acuity (BCVA) of +6.2 ETDRS letters from baseline at 48 weeks. (Image Credit: Adobe Stock/Proxima Studio)

UNITY Biotechnology, Inc. announced positive results from the long-term follow-up of the Phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema (DME). A single injection of UBX1325 treatment led to a statistically significant improvement in vision lasting for the duration of the study (48 weeks), marked by a gain of +6.2 ETDRS letters from baseline, representing a difference of +5.6 ETDRS letters compared to sham-treated patients. In addition, patients treated with UBX1325 maintained stable CST compared to worsening in sham-treated patients.

"This is a defining moment for the senolytic therapeutic hypothesis and is a pivotal moment for UNITY. Achieving sustained improvements in visual acuity and stabilization of retinal structure for almost 1 year after a single injection of UBX1325 is a remarkable result," said Anirvan Ghosh, Ph.D., chief executive officer of UNITY. "UBX1325 is the only treatment candidate in clinical development that targets senescent cells to potentially modify the course of disease, and this therapeutic approach could redefine the standard of care in DME. Based on the strong emerging clinical profile of UBX1325, we are planning to move forward with our Phase 2b DME head-to-head study against aflibercept in the second half of 2023."

The BEHOLD study enrolled patients who, despite being on anti-VEGF treatment for at least 6 months, displayed persistent visual acuity deficits and residual retinal fluid. At baseline, patients in the study had an average visual acuity of 61.4 ETDRS letters and a CST of approximately 439.6 microns. In the 6 months prior to study enrollment, patients received an average of 4 anti-VEGF injections, with the last anti-VEGF injection occurring 3-6 weeks prior to randomization. Fifty patients completed the 48-week study extension.

48-Week Phase 2 BEHOLD Data:

UBX1325 demonstrated a favorable safety and tolerability profile with no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis, or vasculitis

Patients treated with UBX1325 had a mean change in BCVA of +6.2 ETDRS letters from baseline to 48 weeks (p=0.0037), representing a difference of +5.6 ETDRS letters compared to sham-treated patients (p=0.1198)

Based on an analysis of the BCVA change from baseline to last observation before anti-VEGF rescue or end of study participation, UBX1325 showed a +7.6 ETDRS letter advantage over sham (p = 0.0007)

Approximately 53% of UBX1325-treated patients went 48 weeks without requiring any anti-VEGF rescue treatment compared to only 22% of patients in the sham arm

Patients treated with UBX1325 had a mean change in CST of -16.6 microns from baseline at 40 weeks, representing an improvement compared to sham of -56.3 microns (p = 0.0479); at 48 weeks, UBX1325 had a mean change of -13.7 microns representing an improvement of -37.9 microns compared to sham (p = NS, in part due to the low number of sham patients remaining rescue-free at 48 weeks).

"DME patients are challenging to treat, often requiring frequent injections to decrease retinal edema and improve or even maintain vision. In this study, UBX1325 achieved visual improvement with a single injection, and maintained this improvement in over 50% of patients for a year," said Jeffrey S. Heier, M.D., Director of Retina Research at Ophthalmic Consultants of Boston. "UBX1325, with a novel mechanism of action, could be an important therapeutic option for patients with such a complex, multifactorial disease."