Protalix BioTherapeutics announced positive preliminary results from its Phase 1 first-in-human study of PRX-115, a PEGylated uricase being developed for uncontrolled gout. The study, presented at the American College of Rheumatology (ACR) Convergence 2024, demonstrated that PRX-115 was well-tolerated and exhibited dose-dependent urate-lowering responses.
The Phase 1 trial (NCT05745727) enrolled 64 participants, with 48 receiving PRX-115 and 16 receiving a placebo. Participants had mean urate levels ranging from 7.0-8.5 mg/dL at baseline and were followed for 85 days. The primary endpoint was safety and tolerability, while secondary endpoints included pharmacokinetic and pharmacodynamic assessments.
Safety and Tolerability
The study found that treatment emergent adverse events (TEAE) rates were similar between the PRX-115 (77.1%) and placebo (81.3%) groups. Most adverse events related to the study drug were mild to moderate and transient. One participant experienced an anaphylactic reaction early in the infusion, which resolved completely after treatment. Subsequent participants received anti-histamine and steroid premedication, and no similar reactions were reported.
Urate-Lowering Efficacy
PRX-115 exposure increased in a dose-dependent manner, with maximal concentrations generally observed immediately post-infusion. The drug remained detectable in plasma for up to 12 weeks in the highest dose cohorts. A single dose of PRX-115 rapidly reduced plasma urate levels across all dose levels. Notably, at the highest dose levels, mean plasma urate levels remained below 6.0 mg/dL for up to 12 weeks.
Mechanism of Action
PRX-115 works by catalyzing the breakdown of urate into allantoin, a more soluble compound that is easily excreted. The PEGylation is designed to improve stability, increase half-life, reduce immunogenicity, and maintain high specific activity.
Future Directions
"We are pleased to report that all 8 cohorts of our phase I first-in-human study of PRX-115, our recombinant uricase candidate being developed for the treatment of uncontrolled gout, are now complete," said Dror Bashan, President and Chief Executive Officer, Protalix. "Preliminary results from this study are encouraging and demonstrate the potential of PRX-115 to be a promising uric-acid lowering treatment option for individuals with gout. We are actively planning a phase II clinical trial of PRX-115 in gout patients and expect to initiate the study in the second half of 2025."
The investigators concluded that PRX-115 may offer an effective urate-lowering treatment with a potentially wide dosing interval, which may enhance patient compliance and treatment flexibility.
