Unity Biotechnology, Inc. announced results from Part A of the Phase 2 ENVISION study of UBX1325 in patients with wet age-related macular degeneration (AMD) who were not achieving optimum benefit with their ongoing anti-VEGF therapy. UBX1325 treatment generally maintained visual acuity for 6 months (change of -0.8 ETDRS letters from baseline), with a majority of patients not requiring any anti-VEGF rescue. Patients in the every 8-week aflibercept arm had an early and unexpected gain of 3.5 letters at week 2 which was mostly maintained for the duration of the study.

As a result of the strength on the control arm, the study did not meet the non-inferiority threshold compared to aflibercept through 24 weeks. The ENVISION study enrolled 51 patients with an average baseline visual acuity of 60.2 ETDRS letters who had ongoing active disease with a baseline CST of approximately 370 µm and had been on anti-VEGF treatment for at least 6 months. On average, patients received approximately 4 anti-VEGF injections in the 6 months prior to enrollment.

At enrollment, all patients received a single run-in injection of aflibercept. Within 4-8 weeks following the run-in injection, patients were randomized to receive either (a) an injection of UBX1325 at week 0 and at week 4, or (b) an injection of aflibercept at week 0 and every 8 weeks thereafter, and followed for 24 weeks. Phase 2 ENVISION data through 24 weeks: UBX1325 demonstrated a favorable safety and tolerability profile with no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis, or vasculitis Patients treated with UBX1325 had a mean change from baseline in BCVA of -0.8 ETDRS letters at 24 weeks compared to +3.1 ETDRS letters in the aflibercept control arm Patients treated with UBX1325 had a mean change from baseline in CST of +87.3 µm at 24 weeks compared to +30.5 µm in the aflibercept control arm 52% of UBX1325-treated patients went at least 24 weeks without receiving anti-VEGF treatment; 92% of UBX1325-treated patients achieved a maximal anti-VEGF treatment-free interval of 12 weeks or longer The ENVISION study did not meet the non-inferiority margin of -4.5 letters compared to aflibercept with an 85% confidence interval.

The proof-of-concept Phase 2 ENVISION study is a multi-center, randomized, double-masked, active-controlled study designed to evaluate the safety, tolerability, efficacy and durability of a repeat intravitreal injection of UBX1325 in patients with neovascular AMD evaluated though 24 weeks. The study enrolled 51 patients being actively treated with anti-VEGF who had a visual acuity deficit (73 ETDRS letters, approximately 20/40, or worse) and residual retinal fluid (CST =300 microns). Patients were randomized into two groups to receive either two 10 mcg doses of UBX1325 at a week 0 and at week 4 or aflibercept 2 mg every 8 weeks.

Patients have the option of continuing in the long-term extension (Part B) portion of the study through 48-weeks. To date, a majority of patients have opted to remain in the study. More information about the study is available here (NCT05275205).