UNITY announces positive diabetic macular edema study results

Single injection of senolytic therapy UBX1325 led to a statistically significant and clinically meaningful improvement in Best Corrected Visual Acuity.

UNITY Biotechnology, a company working on therapeutics to slow, halt or reverse diseases of aging, today announced positive results from the long-term follow-up of the Phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema (DME).

UBX1325 is an investigational compound being studied for age-related diseases of the eye, including diabetic macular edema (DME), age-related macular degeneration (AMD), and diabetic retinopathy (DR).

A single injection of UBX1325 treatment led to a statistically significant improvement in vision lasting for the 48-week duration of the study, marked by a gain of +6.2 ETDRS letters from baseline, representing a difference of +5.6 ETDRS letters compared with sham-treated patients. In addition, patients treated with UBX1325 maintained stable CST compared with worsening in sham-treated patients [1].

Longevity.Technology: Senescent cells are cells that have reached the end of their replication lifespan, or have been damaged beyond repair, but which have ‘forgotten’ to undergo apoptosis or cell death. Instead, they remain in the body, accumulating over time, encouraging other cells to become senescent and contributing to age-related diseases and impairments.

Senescent cells also secrete a toxic mix of of inflammatory cytokines, growth factors and proteases (senescence-associated secretory phenotype or SASP). SASP can promote chronic inflammation, tissue remodeling and other changes that can drive the development and progression of age-related diseases.

Senolytics selectively eliminate senescent cells from the body, meaning they have the potential to alleviate age-related diseases and improve healthspan; senolytics have been shown to improve tissue function and reduce inflammation in animal models of aging [2], so understandably, there is growing interest in developing these drugs for human use. UNITY is showing that when it comes to senolytic therapy, it certainly has its eyes on the prize.

UBX1325 is a potent small molecule inhibitor of Bcl-xL, a member of the Bcl-2 family of apoptosis-regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival.

UNITY Biotech announces positive results from Phase 2 BEHOLD study on diabetic macular edema

“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, PhD, 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 [1].”

The BEHOLD study enrolled 65 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 [1].

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 with 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 with 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 with 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 with 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,” said Jeffrey S Heier, MD, Director of Retina Research at Ophthalmic Consultants of Boston. “In this study, UBX1325 achieved visual improvement with a single injection, and maintained this improvement in over 50% of patients for a year.

“UBX1325, with a novel mechanism of action, could be an important therapeutic option for patients with such a complex, multifactorial disease [1].”