UNITY Biotechnology was one of the first senolytics companies, and now conducts clinical trials of small molecule senolytic therapies based on well-established mechanisms by which senescent cells can be selectively forced into programmed cell death. The company has consistently pursued a strategy of delivering senolytic drugs locally to affect only specific diseased tissue, and has been criticized for doing so. Firstly such drugs will have limited off-label uses, and secondly for at least some conditions it seems plausible that local senescent cells are only part of the problem. There are many more senescent cells elsewhere in the body, and their signaling still contributes to inflammation in the affected organ. Still, it seems that UNITY's macular edema program has achieved better results in clinical trials than the program for knee osteoarthritis.
UNITY Biotechnology, Inc., a biotechnology company developing therapeutics to slow, halt or reverse diseases of aging, today announced topline results from the Phase 2b ASPIRE clinical trial of intravitreal UBX1325 in patients with diabetic macular edema (DME) who had poor vision despite prior anti-VEGF treatment. UBX1325 is a novel BCL-xL inhibitor that is designed to eliminate senescent cells in diabetic retinal blood vessels, while leaving healthy ones intact. UBX1325 is administered via intravitreal injections that are standard procedure in clinical practice, minimizing treatment complexity and reducing the challenges of adapting to other technologies or surgical procedures.
Of the 1.7 million people in the U.S. with DME, approximately 750,000 patients have been diagnosed and are being treated. For the last 20 years, the standard of care for DME treatment has been anti-VEGF-related agents such as aflibercept. Despite vision improvements and stabilization with anti-VEGF therapy, one half of patients have a sub-optimal response and discontinue treatment after 6 months. For those that do respond, their vision gains generally plateau after 24 months of treatment and eventually start to decline despite cycling through different anti-VEGF treatment options.
The study results include data from all patients through 24 weeks, and the majority of patients through 36 weeks. UBX1325 treatment led to visual acuity gains of over 5 letters from baseline at weeks 24 and 36, and achieved non-inferiority to aflibercept at 9 out of 10 time points through 36 weeks, except for the average of weeks 20 and 24, where it achieved non-inferiority at an 88% confidence interval (compared to a 90% threshold pre-specified as primary analysis endpoint). UBX1325 continues to demonstrate a favorable safety and tolerability profile across multiple clinical studies to date. There have been no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis or vasculitis across multiple studies.
View the full article at FightAging
