UBX1325 fails to meet noninferiority endpoint but performs better in longer-duration AMD
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SEATTLE — In the phase 2 ENVISION trial, UBX1325 failed to meet the primary endpoint of noninferiority to aflibercept in wet age-related macular degeneration but showed comparable outcomes in a subgroup of advanced cases.
The results of part A of this proof-of-concept study were presented at the American Society of Retina Specialists annual meeting by Raj Maturi, MD, who explained that UBX1325 (foselutoclax, Unity Biotechnology) inhibits the function of specific profibrotic, proinflammatory factors in senescent cells.
“Senescent cells are no longer dividing, stressed, but metabolically active cells that drive disease pathology,” he said.
In the study, 51 patients received one dose of aflibercept at baseline and were then randomly assigned to receive UBX1325 for two doses with a 4-week interval or aflibercept every 8 weeks.
UBX1325 was found to be safe and well tolerated, with no signs of intraocular inflammation, and 52% of patients did not require anti-VEGF treatment through 24 weeks.
However, “UBX1325 monotherapy did not achieve noninferiority through week 24 due in part to an unexpected 3.5 letter gain in the anti-VEGF control arm,” Maturi said.
While the aflibercept arm showed significant improvement in the first 2 weeks that was maintained through 24 weeks, in the UBX1325 arm, baseline vision was maintained but did not improve, and mean central subfield thickness did not decrease.
A secondary post hoc analysis suggested that UBX1325 may be more effective in patients with longer disease duration, “as they may have a larger senescence burden,” Maturi said. In the subgroup of patients with AMD diagnosed for more than 2 years, there was no difference in best corrected visual acuity change between the two groups in terms of letter gain.
Exploratory multifocal electroretinogram analysis is underway. Data are still masked, but overall improvement in photoreceptor function has been seen at 1 year.
“Part B of the ENVISION study is exploring the potential benefit of this drug as a combination treatment with anti-VEGF,” Maturi said.
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Maturi R. Results of the phase 2 ENVISION trial of UBX1325, a novel investigational senolytic agent for wet AMD. Presented at: American Society of Retina Specialists annual meeting; July 28-Aug. 1, 2023; Seattle.
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