UBX1325 Matches Aflibercept in Vision Gains for DME at 36 Weeks

UNITY Biotechnology has announced favorable results from the 36-week Phase 2b ASPIRE study, which indicated that UBX1325 (foselutoclax) demonstrated noninferior vision gains compared with aflibercept for diabetic macular edema (DME) across 36 weeks.1

Announced on May 5, 2025, UBX1325 is an as-yet unapproved small-molecule inhibitor of BCL-xL, a type of apoptosis-regulating protein. UBX1325 inhibits the function of proteins that senescent cells rely on for survival. Preclinical studies have indicated that targeting BCL-xL with UBX1325 eliminated senescent cells from diseased tissue without affecting healthy tissue.1

“UBX1325 has demonstrated the potential to provide a much-needed alternative treatment to anti-VEGF therapy through a completely novel mechanism of action,” said Anirvan Ghosh, PhD, chief executive officer of UNITY. “UBX1325’s demonstration of non-inferiority to aflibercept at 36 weeks and superior vision gains in the subgroup of patients with CST under 400 microns underscores its potential to provide a valuable treatment option to patients.”1

ASPIRE was a prospective, multicenter, randomized, double-masked, active-controlled study that began in August 2023, including 52 patients aged ≥18 years with nonproliferative diabetic retinopathy (DR) and DME. All patients had center-involved DME with central subfield thickness (CST) ≥325-900 µm and best-corrected visual acuity (BCVA) in the study eye of 70-30 Early Treatment Diabetic Retinopathy Study (ETDRS) letters.2

Patients received 3 run-in injections of aflibercept roughly 4 weeks apart, with the last injection occurring 4-6 weeks before the first day of the study. At the beginning of the trial, participants were randomized into two arms: the active comparator arm, receiving intravitreal 2 mg aflibercept on day 1 and weeks 8 and 16, and the experimental arm, receiving intravitreal 10 µg UBX1325 on day 1 and weeks 8 and 16.2

Primary efficacy outcomes of ASPIRE included changes in BCVA, CST, and ETDRS gains from baseline to week 36. Safety was measured by taking the percentage of participants with ≥1 treatment-emergent adverse effect (TEAE) in the study or fellow eye.2

Early results indicated that participants in ASPIRE exhibited non-inferior visual gains in BCVA compared to aflibercept. UBX1325 outperformed aflibercept in subjects with moderately aggressive disease (CST <400 microns at baseline or first run-in). UBX1325 treatment led to BCVA gains of >5 letters from baseline at weeks 24 and 36, indicating non-inferiority to aflibercept at 9 out of 10 points through 36 weeks.1,3

UBX1325 exhibited a favorable safety and tolerability profile across multiple studies, which continued in ASPIRE. No cases of intraocular inflammation, retinal artery occlusion, endophthalmitis, or vasculitis were reported during the study.1

UNITY has expressed interest in collaborating with another company to continue the advancement of UBX1325. This announcement included plans to evaluate strategic alternatives while reducing operational cash burn, with certain consulting arrangements in place to shut down ASPIRE.

Full 36-week results from ASPIRE will be presented at the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.

“We believe that further development of UBX1325 would benefit from the capabilities of a company with an existing ophthalmic franchise, and we are exploring partnerships so that this program can continue to be advanced as a potential new treatment,” said Ghosh. “I am proud of the valuable contributions our team has made in advancing a new therapeutic concept for DME, as featured in our recently published article in NEJM Evidence.”1

References

1. UNITY Biotechnology Announces Complete 36-Week Results from the ASPIRE Phase 2b Study of UBX1325 in Diabetic Macular Edema and Provides Corporate Updates. GlobeNewswire by notified. 5 May 2025. Accessed 5 May 2025. https://www.globenewswire.com/news-release/2025/05/05/3074007/0/en/UNITY-Biotechnology-Announces-Complete-36-Week-Results-from-the-ASPIRE-Phase-2b-Study-of-UBX1325-in-Diabetic-Macular-Edema-and-Provides-Corporate-Updates.html

2. UNITY Biotechnology, Inc. Study Details: Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients with DME (ASPIRE). Clinicaltrials.gov. September 23, 2024. Accessed May 5, 2025. https://clinicaltrials.gov/study/NCT06011798?term=unity+biotechnology&checkSpell=false&rank=7.

3. UNITY Biotechnology Announces Topline Results from the ASPIRE Phase 2b Study in Diabetic Macular Edema. UNITY Biotechnology. 24 March 2025. Accessed 5 May 2025. https://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-announces-topline-results-aspire-phase-2b