Company says senolytic therapeutic delivers ‘robust vision improvements’ in DME patients despite failing to meet primary endpoint.
Longevity focused biotech company UNITY Biotechnology has released the topline results from its Phase 2b ASPIRE clinical trial evaluating the senolytic therapeutic UBX1325 as a potential treatment for diabetic macular edema (DME). The company, which is developing therapeutics that selectively eliminate or modulate senescent cells to combat age-related diseases, saw its stock price fall around 30% on the news that the trial failed to meet its primary endpoint.
DME is a serious complication of diabetes that occurs when excess fluid accumulates in the macula, causes it to swell, leading to vision problems. While DME is not exclusively an age-related condition, its prevalence and impact are significantly influenced by age and the duration of diabetes.
The current standard of care for DME is anti-VEGF therapies, like Regeneron’s aflibercept, which can pose challenges for patients as adherence can decline over time, potentially reducing their effectiveness. According to UNITY, nearly half of all patients do not achieve optimal results and often discontinue therapy within six months.
UBX1325 targets senescent cells in the retinal blood vessels of diabetic patients through inhibition of BCL-xL, a protein that senescent cells rely on for survival. The approach is distinct aims to preserve vision in patients who have had limited success with anti-VEGF therapies.
The trial enrolled 52 patients who had demonstrated poor response to anti-VEGF therapies, the current standard of care. Participants were randomly assigned to receive either 10 μg of UBX1325 or 2 mg of aflibercept every eight weeks for six months.
Results from the trial indicate that UBX1325 narrowly missed the primary endpoint, which was based on the average of weeks 20 and 24, meeting non-inferiority at an 88% confidence interval, just below the pre-specified 90% threshold.
Despite this, UNITY expressed optimism that its therapy provided improvements in visual acuity that were comparable to those achieved with aflibercept, and said that the overall results support the continued development of UBX1325. The treatment demonstrated non-inferiority to aflibercept at 9 out of 10 measured time points through 36 weeks.
“Achieving durable improvements in visual acuity via an entirely new mechanism of action as seen in this study is remarkable and would be invaluable for patients receiving sub-optimal response from current treatment options,” said Dr David S Boyer, adjunct clinical professor of ophthalmology at Keck School of Medicine of USC. “Currently, about half of all patients don’t get optimal results from standard of care treatment and end up cycling through various anti-VEGF-based treatments which do not provide additional vision benefit. UBX1325, if approved, could help patients break out of this burdensome cycle and would be a welcome treatment alternative for patients.”
UNITY also reported that UBX1325 showed numerical superiority to aflibercept at seven out of ten time points in a subset of patients with moderately aggressive disease.
“We are excited that UBX1325 showed robust vision improvements in a difficult to treat patient population,” said CEO Dr Anirvan Ghosh. “The results also suggest that UBX1325 may provide greater vision gains than standard of care in patients with moderately aggressive disease. We look forward to advancing UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies.”
UNITY anticipates releasing full 36-week data for all patients in the second quarter of 2025.
