A Senolytic Treatment Improves Visual Function in a Small Trial for Macular Degeneration

UNITY Biotechnology recently reported positive results for their senolytic drug candidate UBX1325, probably derived from navitoclax. Senolytic therapies selectively destroy senescent cells in aged tissues, reducing their inflammatory signaling and contribution to tissue dysfunction. In this case, macular degeneration patients showed improved visual function after treatment, though one should wait for a larger study group before calling this an unqualified success. UNITY Biotechnology's trials are essentially testing the thesis that localized removal of senescent cells can address pathology, and thus low, localized doses of chemotherapeutic-derived senolytic drugs can be used, minimizing side-effects. In this case, the senolytic is injected into the eye.

An earlier trial of localized senolytic administration to arthritic knee joints failed to show meaningful benefits in patients, which led to some discussion in the community over whether or not localized delivery of senolytics could ever work. Is the contribution of inflammatory senescent cell signaling elsewhere in the body sizable enough to continue to cause issues after the local population is removed? UNITY Biotechnology will clearly be continuing to a larger study for macular degeneration, so we shall see if the results continue to look promising.

UNITY Biotechnology, Inc. ("UNITY"), a biotechnology company developing therapeutics to slow, halt, or reverse diseases of aging, today announced 24-week data from its Phase 1 single ascending dose (SAD) safety study of UBX1325 in patients with advanced disease from diabetic macular edema (DME) or wet age-related macular degeneration (AMD). A majority of patients with DME across all doses had rapid improvements in vision, and patients in the higher dose cohorts showed a mean gain of 9.5 ETDRS letters in best-corrected visual acuity (BCVA) at 24 weeks following a single injection of UBX1325. Similarly, a majority of wet AMD patients treated with UBX1325 showed rapid gains in visual acuity, which were maintained through 12 weeks. In most patients, central subfield thickness (CST) remained stable through the study period.

The study enrolled a total of 19 patients with advanced DME (n=8) and wet AMD (n=11) for whom anti-VEGF therapy was no longer considered beneficial. UBX1325 was well-tolerated at all doses tested (through 10 mcg) with no dose-limiting toxicities and no reported incidence of inflammation. The Phase 1 data show rapid improvements in visual acuity as measured by BCVA in patients with DME, with the majority of patients demonstrating sustained responses through 24 weeks.

"A 10 letter gain in DME patients, maintained through six months, is an impressive outcome, and is particularly noteworthy considering that it was achieved with a single injection. Hard-to-treat patients require as many as 10 injections in the first year of treatment to see full benefits from currently available anti-VEGF therapies. A treatment that reduces the frequency of injections while showing meaningful and sustained improvements in BCVA would be of huge value for patients and physicians."

Link: https://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-announces-improvement-visual-acuity


REGENXBIO Presents Additional Positive Interim Data from Trials of RGX-314 in Wet AMD and Diabetic Retinopathy Using Suprachoroidal Delivery at AAO 2021
Nov. 12, 2021 4:32 PM ETREGENXBIO Inc. (RGNX)


Different approach than UNITY's. REGENXBIO, AFAI understand, aims to stop AMD progression with an one time anti-VEGF treatment.

Posted by: Jones at November 18th, 2021 5:37 AM

It is not clear how good senolytic are the UBX compounds. We don't know how well do they perform agasint D+Q, fisetin, and navitoclax. Yet along against prodrug conjugate of those.

A similar treatment of proddrug navitoclax followed with some slow release form of rapamycin might perform much better. Unfortunately, those are not easily patentable , therefore not interesting.

Posted by: Cuberat at November 18th, 2021 8:46 AM
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