PolyActiva has announced positive results from its Phase 2 clinical trial of PA5108, a novel implant designed to treat glaucoma by providing sustained drug delivery. The trial achieved its primary efficacy and safety goals, demonstrating a significant reduction in intraocular pressure (IOP) over a 26-week period. This advancement represents a potentially significant improvement in glaucoma management by addressing the common issue of patient non-adherence to traditional eye drop regimens.
The Phase 2 trial involved seventeen participants who received two PA5108 ocular implants, administered 21 weeks apart. Fifteen participants have been monitored for 48 weeks. The data, presented at the Eyecelerator conference and AusBiotechInvest, highlight the implant's ability to consistently deliver medication, mitigating the risk of blindness associated with glaucoma progression.
Sustained Drug Delivery and Biodegradable Design
PA5108 is constructed from a biodegradable polymer designed for sustained drug release. Unlike some other treatments, the PolyActiva implant degrades rapidly after the drug is released, allowing for repeat dosing. According to Michael Coote, MBBS, FRANZCO, clinical professor at the University of Melbourne, the implant releases latanoprost with zero-order kinetics for approximately 26 weeks.
"The implant is delivered to the anterior segment through an easy-to-use delivery device... The implant appears to be mildly adhesive to the iris and is transparent," Coote explained. He also noted that the implant's complete dissolution leaves no residue, a distinct advantage over other options that may remain in the eye after drug depletion.
Encouraging Safety and Efficacy Findings
The Phase 2 trial data indicate encouraging safety and efficacy profiles, with few clinically significant adverse effects observed in implant-treated eyes. "We observed a greater than 20% reduction in IOP based both on 8 AM and mean diurnal IOP readings over the course of the study," Coote stated. In an initial cohort, all eyes receiving a low-dose PA5108 implant experienced the full IOP-lowering effect over 26 weeks. Repeated dosing also showed sustained IOP reduction without evidence of inflammation or corneal endothelial cell changes.
The PA5108 implant delivers therapeutic levels of medication for 26 weeks, confirmed by both dose-delivery studies and therapeutic efficacy based on IOP reduction. This sustained delivery addresses the variability and unpredictability of patient medication adherence, a significant challenge in glaucoma management.
Addressing Challenges in Glaucoma Treatment
Coote highlighted two key areas of importance for glaucoma specialists: prostaglandin orbitopathy and ocular surface disease. The PA5108 implant minimizes the risk of prostaglandin orbitopathy by limiting the amount of active agent seeping into the orbit, unlike topical agents. Additionally, by providing targeted medication delivery, the implant has the potential to reduce adverse effects associated with ocular surface disease, such as dry eye and irritation.
Future Clinical Trials
Building on these results, PolyActiva is preparing for a Phase 2b clinical trial of PA5108. According to Vanessa Waddell, PolyActiva CEO, the company is planning a Phase 2b study in 75 patients, marking their first US study for this product. A clinical study in Australia is also planned to evaluate a second-generation product potentially offering 12 months of treatment. The company anticipates entering Phase 3 trials soon, with hopes of bringing the product to market by 2029.
