Q&A: David Eichenbaum on the outcomes of the ASPIRE Phase 2B Trial

David A. Eichenbaum, MD, FASRS, Director of Research at Retina Vitreous Associates of Florida, presented findings from the ASPIRE phase 2b trial evaluating UBX-1325 (an anti-senolytic agent) compared to aflibercept in diabetic macular edema (DME) at the 2025 American Academy of Ophthalmology meeting. This meeting was held in Orlando, Florida, United States from October 18-20, 2025. In his conversation with Ophthalmology Times Europe, Eichenbaum discussed efficacy outcomes, subgroup analyses, and safety data, emphasizing the evolving treatment landscape in retinal diseases. The he highlighted a shift from monotherapy toward multi-mechanism, personalized therapies for DME and related retinal conditions.

Note: The following conversation has been lightly edited for clarity.

Ophthalmology Times Europe: What were the key efficacy outcomes of the ASPIRE Phase 2B trial comparing UBX1325 with aflibercept in patients with DME, particularly regarding visual acuity and retinal thickness?

David A. Eichenbaum, MD, FASRS: The key efficacy outcome of the ASPIRE phase 2b trial comparing UBX-1325, foselutoclax to aflibercept head-to-head in DME was best-corrected visual acuity, with a primary endpoint being non-inferiority, average of weeks 20 and 24 for the group exposed to UBX-1325, anti-senolytic agent versus aflibercept 2 milligrams.

The results of the ASPIRE phase 2b trial were that Unity's UBX-1325, did not meet its non-inferiority margin to aflibercept 2 milligrams at the primary endpoint, which is the average of weeks 20 and 24. At the end of the study, at week 36 there was non-inferiority between UBX-1325, and aflibercept 2 milligrams. What's important is when you look at the data, and you look at some pre-specified subgroups, patients who had a central subfield thickness of less than 400 microns at the outset of the clinical trial, or who had diabetic macular edema for less than 3 1/2 years, seemed to do better and had many time points, the majority of the time points in which they were showing visual acuity superiority to aflibercept when they were exposed to UBX-1325. That implies that anti-senolytic therapy may have a role in patients with earlier or less severe diabetic macula edema.

OTE: How did the safety and tolerability profile of UBX1325 compare with Aflibercept, and were there any notable adverse events observed?

Eichenbaum: One of the most important things we look at is safety, and there was no intraocular inflammation, retinal vasculitis, or occlusive retinitis in either the group exposed to UBX-1325, or the group exposed to aflibercept 2 milligrams.

OTE: Based on these results, how might UBX1325 influence future treatment strategies for DME, and which patient populations could benefit most from this senolytic approach?

Eichenbaum: One of my take homes from the American Academy of Ophthalmology 2025, is that the era of monotherapy for common retinal disease, especially diabetic eye disease, is probably coming to an end. We are investigating multiple additional mechanisms of action, including foselutoclax anti-senolytic therapy, wnt modulation, anti-inflammatory therapy with biologic inhibition of interleukin 6 in addition to other potent ang2 inhibitors. We're looking at tyrosine kinase inhibition, and we're looking at increasing the durability of delivery with gene therapy. We are seeing a movement, a sea change, away from pulsatile anti-VEGF infections that is going to come with some failures, such as this failure reach primary endpoint for foselutoclax UBX-1325, however, we do learn that senolytic modulation and anti-senolytic therapy may be appropriate for certain patients. It may not be broadly applicable, but we do learn from negative results, just like we learn from positive results, and we are moving the needle on the treatment of diabetic macular edema and other common retinal diseases with multimodal targeting.