PEGylated Uricase Well-Tolerated, Demonstrates Dose-Dependent Urate-Lowering

Orit Cohen-Barak, PhD

PRX-115 (Protalix BioTherapeutics), a PEGylated uricase therapy, was well-tolerated and demonstrated dose-dependent urate-lowering responses in people with gout.¹

These findings, from a first-in-human single ascending dose, double-blinded, study (FIH-SAD, NCT05745727), were presented by Orit Cohen-Barak, PhD, Head of Clinical Development at Protalix, at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC.

PRX-115 catalyzes the breakdown of urate into allantoin, a more soluble and easily excreted compound, and is designed to improve stability and increase half-life, reduce immunogenicity, and maintain high specific activity.

"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," Dror Bashan, President and Chief Executive Officer, Protalix, said in a statement.² "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 study recruited 64 participants randomized to receive placebo (n = 16) or PRX-115 (n = 48). At baseline, the participants had an average age of 35.3 years (standard deviation, 11.9) and were mostly male (n = 43; 67.2%), with mean urate levels ranging from 7.0-8.5 mg/dL. The study participants were followed for 85 days (12 weeks).¹

Cohen-Barak and colleagues found that PRX-115 was well-tolerated, with similar rates of treatment emergent adverse events (TEAE) were similar between the active groups (77.1%; n = 37) and placebo (81.3%; n = 13), with 25% of the active groups (n = 12) reporting study drug related AEs, most of which were mild-to-moderate and transient in nature. One participant in cohort 2 experienced an anaphylactic reaction at the start of infusion (6 minutes) and only received 5% of their applicable PRX-115 dose. The reaction completely resolved, and the participant remains in the safety dataset. Anti-histamine and steroid premedication was implemented after this reaction and no future participants had similar reactions. No other serious AEs were reported during the study.¹

The investigators found that PRX-115 exposure increased in a dose–dependent manner with maximal concentrations observed, in general, immediately post-infusion, and PRX-115 remaining detectable in plasma for up to 12 weeks in cohorts 6, 7 and 8. A single dose of PRX-115 rapidly reduced plasma urate levels at all dose levels. At the highest dose levels, mean plasma urate levels remained below 6.0 mg/dL for up to 12 weeks.¹

“The study results suggest that PRX-115 may offer an effective urate-lowering treatment with an added benefit of a potentially wide dosing interval, which may enhance patient compliance and treatment flexibility,” Cohen-Barak and colleagues concluded.¹

REFERENCES

1. Schwabe C, Cohen-Barak O, Cole A, et al. Prolonged Plasma Urate-Lowering after a Single Intravenous Administration of PRX-115, a Novel PEGylated Uricase, in Participants with Elevated Urate Levels. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L05

2. Protalix BioTherapeutics Reports Third Quarter 2024 Financial and Business Results. News release. Protalix BioTherapeutics. November 14, 2024. https://ir.protalix.com/news-releases/news-release-details/protalix-biotherapeutics-reports-third-quarter-2024-financial