NEJM Publishes UBX1325 DME Phase 2 Results

UNITY Biotechnology has announced that NEJM Evidence has published results from the Phase 2 BEHOLD study, evaluating UBX1325 in patients with diabetic macular edema (DME). The article, titled “Safety and Efficacy of Senolytic UBX1325 in Diabetic Macular Edema,” reports that targeted clearance of senescent cells in the retina provided disease-modifying and long-lasting improvements in vision. These findings support the potential of UBX1325 as a novel therapeutic approach in retinal diseases.

BEHOLD Study Design and Baseline Data

The Phase 2 BEHOLD study was a multi-center, randomized, double-masked, sham-controlled trial assessing the safety, tolerability, efficacy, and durability of a single 10 μg dose of UBX1325 in patients with DME. The study enrolled 65 patients with persistent visual acuity deficits (73 ETDRS letters or worse) and residual retinal fluid (central subfield thickness ≥300 microns), despite being on anti-VEGF therapy for at least 6 months.

At baseline, patients had a mean visual acuity of 61.4 ETDRS letters and a mean CST of approximately 439.6 microns. In the 6 months prior to enrollment, they had received an average of 4 anti-VEGF injections, with the last injection occurring 3–6 weeks before randomization.

Key Findings from BEHOLD and ARVO 2024

At the Association for Research in Vision and Ophthalmology (ARVO) 2024 Annual Meeting, UNITY reported that a single injection of UBX1325 led to a statistically significant and clinically meaningful improvement in vision, with durability extending through 48 weeks in patients with advanced DME.

UNITY’s CEO, Anirvan Ghosh, PhD, stated:

“By targeting senescent cells, we expect to remodel the retinal vasculature, which should lead to improvements in retinal function. We see the impact of this approach in action in the BEHOLD study, in which patients experienced meaningful and sustained improvements in their visual acuity for 1 year after a single injection of UBX1325. By selectively targeting an underlying cause of inflammation and disease progression, senolytic therapies could provide a valuable future treatment option for DME patients.”

Phase 2b ASPIRE Study and Interim Results

UNITY is currently conducting the Phase 2b ASPIRE study, a multi-center, randomized, double-masked, active-controlled trial (NCT06011798) comparing multiple doses of UBX1325 to aflibercept. A total of 52 subjects were randomized 1:1 to receive either 10 μg UBX1325 or 2 mg aflibercept every 8 weeks for 6 months.

Topline data presented on March 24, 2025, showed:

• A mean +5.2 ETDRS letter gain in BCVA at 24 weeks

• A mean +5.5 ETDRS letter gain at 36 weeks

• Non-inferiority to aflibercept through 36 weeks, except for the average at weeks 20 and 24

CST Observations and Supplemental Treatments

The ASPIRE study also noted increases in Central Subfield Thickness (CST) at weeks 16 and 20 in UBX1325-treated patients. These CST changes led to supplemental anti-VEGF treatment in patients with significant CST gains.