Unity's Eye Treatment Falls Short Against Eylea, But Potential Path Forward Remains

Unity Biotechnology's investigational eye treatment, UBX1325, has failed to match Regeneron's blockbuster drug Eylea in a key measure of a mid-stage trial for diabetic macular edema (DME). Despite this setback, analysts see potential paths forward for the experimental therapy.

Trial Results and Market Reaction

The phase 2b Aspire study evaluated UBX1325, a small molecule designed to inhibit BCL-xL, against aflibercept (marketed as Eylea) in 52 patients with previously treated, active DME. The primary endpoint measured non-inferiority compared to aflibercept using the average Best Corrected Visual Acuity (BCVA) letter change from baseline at 20 and 24 weeks.

While UBX1325 showed promise at multiple time points, it fell short at the crucial 20-week mark:

• UBX1325 arm: 3.7 letter gain from baseline
• Aflibercept arm: 5.1 letter gain from baseline

This miss at 20 weeks drove the failure to meet the primary endpoint, despite UBX1325 matching or outperforming aflibercept at other time points. Notably, at 24 weeks, UBX1325 demonstrated a 5.2 letter gain compared to aflibercept's 4.8 letter gain.

The market reacted negatively to the news, with Unity's stock plummeting 33% from $1.82 to $1.20 per share following the announcement.

Potential Paths Forward and Safety Profile

Despite the primary endpoint miss, Unity and analysts see potential paths forward for UBX1325:

1. Performance in specific patient subgroups: UBX1325 showed superiority to aflibercept at seven out of ten time points in a pre-specified population with moderately aggressive disease, representing about 60% of patients.

2. Longer-term data: While complete 36-week treatment data is pending, preliminary results show a 5.5 letter gain for UBX1325 in approximately 75% of patients.

3. Safety profile: UBX1325 demonstrated a favorable safety and tolerability profile, with no reported cases of intraocular inflammation, retinal artery occlusion, endophthalmitis, or vasculitis across multiple studies.

Unity CEO Anirvan Ghosh, Ph.D., expressed optimism about the results, stating, "We are excited that UBX1325 showed robust vision improvements in a difficult to treat patient population. The results also suggest that UBX1325 may provide greater vision gains than standard of care in patients with moderately aggressive disease."

Industry Context and Future Outlook

Unity's setback comes amid broader challenges in the ophthalmology space. On the same day, Australian biotech Opthea reported that its asset also failed to match Eylea in a phase 3 test, raising questions about its future.

Despite these challenges, Unity plans to advance UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies. The company will likely focus on refining its target patient population and leveraging the encouraging safety profile of UBX1325 as it moves forward.

As the landscape for DME treatments continues to evolve, the pharmaceutical industry will be watching closely to see if Unity can overcome this setback and position UBX1325 as a viable alternative to existing therapies.