Design for Phase 2B ASPIRE Study of UBX1325 for DME announced by UNITY

This phase will evaluate UNITY’s UBX1325 (foselutoclax) in a head-to-head comparison with aflibercept for the treatment of diabetic macular edema (DME). (Image Credit: Adobe Stock/Serg Zastavkin)

UNITY Biotechnology, Inc. has designed its Phase 2b ASPIRE clinical trial to evaluate UBX1325 (foselutoclax) head-to-head against aflibercept. The study design will include participants with active diabetic macular edema (DME) who have been previously treated but are not achieving optimal benefit from standard of care.¹

The company plans activate clinical trial sites in the third quarter and dose the first patients with UBX1325 in the fourth quarter of 2023.

Anirvan Ghosh, PhD, chief executive officer of UNITY elaborated on the design and excitement for its potential in the press release, “The Phase 2b ASPIRE Study is designed to provide a clear and robust comparison between UBX1325 and the standard of care aflibercept in a head-to head trial in patients with DME. Participants in the study drug arm will receive three doses of UBX1325 over the duration of the study, in a frequency that mirrors the real-world dosing schedule in the aflibercept arm. Based on the significant improvement in vision and durable effect observed with UBX1325 in our Phase 2 BEHOLD study, we are excited to explore the potential benefit of UBX1325 as a monotherapy in patients with DME who are no longer benefiting from standard anti-VEGF therapy.”

ASPIRE Trial Design

The Phase 2b ASPIRE study is a multi-center, randomized, double-masked, active-controlled study designed to evaluate the safety and efficacy of UBX1325 in comparison to aflibercept. Patients will be randomized 1:1 to receive either 10 μg UBX1325, or 2 mg of aflibercept control injections every eight weeks for six months.

• The study will enroll participants with non-proliferative diabetic retinopathy (NPDR) who have residual visual acuity deficits and excess fluid in the retina despite having received at least three anti-VEGF injections in the preceding six months.
• All participants will receive three doses of 2 mg aflibercept as a “run-in” prior to randomization.
• The study will enroll approximately 40 participants, with 20 participants per arm, who have plateaued in their anti-VEGF response and are no longer receiving optimal benefit from standard of care treatment.
• The primary efficacy endpoint will be mean change from baseline in Best Corrected Visual Acuity (BCVA) to week 24.
• Secondary endpoints will include change in BCVA over time, and CST change from baseline to week 24.

UNITY will begin activating clinical trial sites in the ASPIRE study in Q3 2023 and expects the first patient to be dosed in Q4 2023. With current timelines, last patient visit is expected to be in Q4 2024, with 16- and 24-week data readouts anticipated in Q1 2025.

About UBX1325

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) that is not approved for any use in any country. 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. The Phase 2 BEHOLD study in patients with DME demonstrated that a single injection of UBX1325 resulted in a statistically significant and clinically meaningful improvement in mean Best Corrected Visual Acuity (BCVA) through 48 weeks compared to sham treatment. In preclinical studies, UNITY has demonstrated that targeting Bcl-xL with UBX1325 preferentially eliminated senescent cells from diseased tissue while sparing cells in healthy tissue. UNITY’s goal with UBX1325 is to transformationally improve real-world outcomes for patients with DME, AMD, and DR.

Reference:

1. UNITY Announces Design of Phase 2b ASPIRE Study Evaluating UBX1325 in Diabetic Macular Edema (DME). Unity Biotechnology, Inc. June 21, 2023. Accessed June 22, 2023. https://www.globenewswire.com/news-release/2023/06/21/2691854/0/en/UNITY-Announces-Design-of-Phase-2b-ASPIRE-Study-Evaluating-UBX1325-in-Diabetic-Macular-Edema-DME.html