Unity to focus on UBX1325 in diabetic macular edema
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Key takeaways:
- UBX1325 with aflibercept in wet AMD maintained 24-week vision gains through 48 weeks.
- Unity is directing resources for UBX1325 toward its diabetic macular edema program.
Patients with wet age-related macular degeneration who were switched from aflibercept alone to a combination of aflibercept and UBX1325 at week 24 maintained vision gains through 48 weeks in part B of the phase 2 ENVISION study.
“The ENVISION study shows that patients with wet AMD who switch from anti-VEGF to UBX1325 can maintain visual acuity with a significant reduction in anti-VEGF treatment burden,” Anirvan Ghosh, PhD, CEO of Unity Biotechnology, said in a press release. “Patients with more severe disease may benefit from a combination of aflibercept and UBX1325.”
Image: Adobe Stock
However, Ghosh said that Unity is now directing its resources toward the diabetic macular edema program, which achieved a statistically significant improvement in visual acuity with UBX1325 monotherapy in the phase 2 BEHOLD study.
In a prespecified subgroup in part B of the ENVISION study, patients with visual acuity of 60 ETDRS letters or less at baseline gained 3.2 ETDRS letters with the combination treatment between weeks 24 and 48.
In the UBX1325 monotherapy arm, patients gained 0.1 ETDRS letters at 24 weeks but lost 1.5 ETDRS letters at 48 weeks.
Forty percent of patients treated with UBX1325 did not need anti-VEGF rescue through 48 weeks, and 64% achieved an anti-VEGF treatment-free period of more than 24 weeks, with the median time to first anti-VEGF rescue being 32 weeks.
UBX1325 was safe and well tolerated when delivered as monotherapy or in combination with aflibercept, with no reports of significant intraocular inflammation, retinal artery occlusion or endophthalmitis.
Perspective
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Unity Biotechnology completed the phase 2 ENVISION study of UBX1325 (foselutoclax) in patients with wet age-related macular degeneration.
The ENVISION study was a proof-of-concept study of UBX1325 in patients with wet AMD. UBX1325 selectively inhibits senescent cells, which are implicated in diseases such as wet AMD and diabetic macular edema.
In the ENVISION study, 51 patients received one dose of aflibercept at baseline and then were randomly assigned to receive either UBX1325 for four doses at day 1, week 4, week 24 and week 28 (monotherapy arm) or aflibercept 2 mg control given every 8 weeks with a dose of UBX1325 added to weeks 24 and 32 (combination arm).
Key takeaways:
- UBX1325 continues to be well tolerated in both monotherapy and combination arms.
- Forty percent of patients in the UBX1325 monotherapy arm did not require anti-VEGF rescue treatment through 48 weeks.
- Patients randomized to UBX1325 monotherapy maintained visual acuity (excluding post-rescue data).
- Patients in the combination arm maintained vision gains achieved at week 24 with aflibercept alone, with greater vision improvement seen in patients with more severe disease.
Although in part A of ENVISION UBX1325 did not achieve noninferiority to aflibercept, there were comparable outcomes in subgroups of advanced disease. Part B showed that patients with more severe disease (lower baseline best corrected visual acuity and higher baseline central subfield thickness) in the combination arm had greater vision improvements.
It was encouraging to learn that patients switching from anti-VEGF (with a mean of four intravitreal injections in the preceding 6 months prior to enrollment) to UBX1325 maintained visual acuity with a significant reduction in anti-VEGF burden.
Anti-VEGF therapies remain the mainstay treatment for wet AMD. However, there is still an unmet need, especially in certain wet AMD patients whose response to anti-VEGF is inadequate despite treatment. For these patients, an add-on, orthogonal therapy may be appropriate. The combination of UBX1325 and aflibercept may provide meaningful visual acuity gains in patients with significant visual deficit despite prior anti-VEGF treatment.
In DME (BEHOLD study), UBX1325 vs. sham control showed a gain of 6.2 letters from baseline in the UBX1325-treated patients (excluding post-rescue data). AMD is a more acute and aggressive disease characterized by focal deregulation of endothelial cells and growth of blood vessels (concentrated heavy burden of senescent cells in the area of disease activity). DME is a more protracted disease with preclinical modeling suggesting a diffuse burden of senescent cells (senescent cells spread throughout retinal vascular beds). Hence, clearance of senescent cells in DME may lead to sustained improvements.
Unity is currently enrolling patients with DME in the phase 2b ASPIRE study, evaluating a repeat dose of UBX1325 vs. aflibercept 2 mg given every 8 weeks.
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