Jennifer Nadelmann, MD
Weill Cornell Medicine
At the 11th Annual Vit-Buckle Society meeting on April 14th Dr. Michael Singer presented “Results of the Phase 2 ENVISION Trial of UBX1325, a novel investigational senolytic agent for Wet AMD.” He first began his talk by discussing mechanism of action of UBX1325, which targets senescent cells that are associated with advanced AMD.
He then discussed the UBX1325 Phase 2 ENVISION Study and provided the 24-week data in patients with wet AMD. The study endpoints included safety and tolerability, best corrected visual acuity (BCVA) change from baseline, central subfield thickness (CST) change from baseline, non-inferiority vs. aflibercept, durability of response, sub- and intra-retinal fluid, changes in perfusion and changes in photoreceptor function. The study population included patients with AMD who had at least 2 anti-VEGF intravitreal injections in the preceding 6-month period, BCVA of 70-20 EDTRS letters and active choroidal neovascularization with sub- and/or intra-retinal fluid. UBX1325 was dosed at 0 and 4 weeks while aflibercept was dosed at 0, 8 and 16 weeks.
He showed that while UBX1325 patients maintained BCVA through 24 weeks, non-inferiority was not met. When excluding post-rescue data, he showed that there was a delayed impact on CST. When including post-rescue data, anti-VEGF rescue appeared to improve CST in UBX1325-treated patients. He reported that patients with an AMD diagnosis over 2 years may have a stronger treatment effect with UBX1325 since the results were similar between UBX1325 and aflibercept treated patients with an AMD diagnosis of more than 2 years. When looking at the durability of effect of UBX1325 he showed that 52% of patients avoided anti-VEGF treatment for at least 6 months. In addition, he reported that UBX1325 was generally well tolerated. Part B on the ENVISION study will be exploring a potential benefit of UBX1325 in combination with anti-VEGF compared to UBX1325 alone, investigating whether there may be a combination pathway.