Unity Biotechnology’s investigational eye treatment failed to match Eylea at 20 weeks—part of the mid-stage trial’s primary endpoint and the only time stamp out of 10 in which the candidate was inferior to Regeneron’s blockbuster.
Despite the miss, Mizuho analysts still highlighted possible paths forward for the candidate in a March 24 note.
Investors didn't appear to be buying this optimistic outlook, sending Unity’s stock sliding 33% from $1.82 per share at market close last Friday to $1.20 as of 11 a.m. ET Monday.
The topline results come from the California company’s phase 2b study, dubbed Aspire, which is evaluating intravitreal UBX1325, a small molecule designed to inhibit BCL-xL. The double-masked trial enrolled 52 patients with previously treated, active diabetic macular edema (DME).
Participants were randomized to receive either 10 μg of UBX1325 or 2 mg of aflibercept—sold under brand names Eylea and Zaltrap—every eight weeks for six months.
The study missed the primary endpoint, which measured non-inferiority compared to aflibercept using the average Best Corrected Visual Acuity (BCVA) letter change from baseline at 20 and 24 weeks.
Across the 20- to 24-week average, patients in the UBX1325 arm gained 3.7 letters from baseline versus a 5.1 gain for patients in the control arm. The 88% confidence interval narrowly missed the 90% pre-specified threshold.
While the combined measure was the study’s main endpoint, the miss was driven fully by the 20-week data, which was the only measure out of 10 across 36 weeks in which UBX1325 was inferior to aflibercept.
At 24 weeks, the investigational treatment was tied to a 5.2 letter gain in visual acuity, compared to 4.8 in the control arm.
Though complete data for 36-week treatment is expected later this quarter, a 5.5 letter gain was recorded for the patients (about 75% of total) included so far.
Furthermore, the biotech’s data found that UBX1325 was actually superior to aflibercept at seven of the 10 time points in a pre-specified population with moderately aggressive disease. The population represents about 60% of patients and is a group Mizuho analysts flagged as a potential path forward for the drug.
“We are excited that UBX1325 showed robust vision improvements in a difficult to treat patient population,” Unity CEO Anirvan Ghosh, Ph.D., said in a March 24 release. “The results also suggest that UBX1325 may provide greater vision gains than standard of care in patients with moderately aggressive disease. We look forward to advancing UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies.”
The investigational treatment demonstrated a favorable safety and tolerability profile, with no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis or vasculitis reported across multiple studies, according to Unity.
Mizuho analysts pointed to the primary endpoint measure likely favoring aflibercept, more prior Vabysmo patients in the investigational arm and a longer average time of DME diagnosis for the UBX1325 arm as all possibly contributing to the study’s primary endpoint fail.
Previously, Unity tested out UBX1325 in wet age-related macular degeneration—also against Eylea. The candidate passed the main goal of a phase 2 trial that measured safety but failed to significantly improve vision for all patients when compared to the Regeneron blockbuster.
It’s a great day for Regeneron as Unity is the second biotech to report a miss against its eye injection. Just this morning, Australia-based Opthea’s asset failed to match Eylea in a phase 3 test, leaving the biotech to question its own future.