Unity Biotechnology Announces Positive 24-Week Data from Phase 2 BEHOLD Study of UBX1325 in Patients with DME

Unity Biotechnology announced that the key safety and efficacy endpoints were met at 24 weeks in the phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema (DME). The company intends to initiate a pivotal study in DME in the second half of 2023.

At 24 weeks after a single dose of UBX1325, the mean change in BCVA of UBX1325-treated subjects was an increase of +6.2 ETDRS letters, representing an improvement of +7.6 ETDRS letters compared to sham-treated subjects from baseline (P=0.0084). In addition, patients treated with UBX1325 maintained CST compared to sham-treated patients who demonstrated worsening of CST (i.e., increased retinal thickness) through 24 weeks. Of patients treated with UBX1325, 59.4% did not require anti-VEGF standard of care through 6 months, as compared to only 37.5% of sham-treated patients.

“It is remarkable to see such clinically meaningful and sustained improvements in vision after a single injection of UBX1325 in patients who had reached a therapeutic plateau with anti-VEGF treatment,” said Anirvan Ghosh, PhD, chief executive officer of Unity. “In today’s treatment paradigm for DME, most patients require frequent injections—and still a large proportion of patients with the current standard of care have residual visual deficits. Based on the results of this study we believe UBX1325 could lead to significant vision gain while reducing treatment burden for patients. The durable effect we’ve now observed through 6 months following just a single injection of UBX1325 suggests it could represent a longer-lasting, disease-modifying treatment option for patients.”

Patients enrolled in BEHOLD had been on anti-VEGF treatment for at least 6 months prior to enrollment into the study (mean injection frequency of 4 in the preceding 6 months), with the last anti-VEGF injection occurring 3-6 weeks prior to randomization.

Evidence of favorable safety, visual acuity improvement, and structural stability in a difficult-to-treat patient population at 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 a single injection of UBX1325 had a mean improvement in BCVA of +7.6 letters compared to sham (P=0.0084). UBX1325-treated patients gained +6.2 ETDRS letters from baseline compared to a loss of -1.4 ETDRS letters in sham-treated patients

• Patients treated with UBX1325 had a mean change in CST of -5.4 microns from baseline compared to an increase (worsening) of +34.6 microns in sham-treated patients for a total difference of 40.0 microns (P=0.1244)
   
• 59.4% of UBX1325-treated patients went 6 months without receiving any anti-VEGF rescue compared to 37.5% of sham-treated patients

“A 7.6-letter gain in BCVA from baseline in UBX1325-treated patients who had visual deficits and retinal fluid despite being on anti-VEGF treatment is a clinically meaningful and impressive outcome,” said Arshad M. Khanani, MD, MA, Director of Clinical Research at Sierra Eye Associates. “A potential treatment with a novel mechanism of action that provides significant and durable gain in vision would be of great value to patients with DME.”

Jamie Dananberg, MD, chief medical officer of Unity added, “We believe we have altered the disease trajectory of patients treated with UBX1325, as evidenced by the 24-week results. Observing significantly greater letter gains and stabilization of retinal structure compared to the sham arm after a single injection of UBX1325 is encouraging and speaks to the potential of disease modification with a senolytic treatment. We look forward to further evaluating the durability of treatment effect through 48 weeks with our long-term extension of the BEHOLD study.”

Upcoming Clinical Milestones for UBX1325

• 48-week long-term safety and efficacy data from phase 2 BEHOLD study in DME expected in Q2 2023
   
• 16-week safety and efficacy data from phase 2 ENVISION study in wet age-related macular degeneration (AMD) expected in Q1 2023, and 24-week safety and efficacy data expected in Q2 2023

About the BEHOLD Study

The proof-of-concept phase 2 BEHOLD study is a multicenter, randomized, double-masked, sham-controlled study designed to evaluate the safety, tolerability, efficacy and durability of a single 10 mcg dose of UBX1325 in patients with DME evaluated though 24 weeks. The study enrolled 65 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 have the option of continuing in the long-term extension 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 (NCT04857996).