Prolonged plasma urate-lowering with a novel pegylated uricase

The PEGylated uricase PRX-115 demonstrated fast urate-lowering effects in patients with gout, who tolerated this therapy well. The response and its duration were dose-dependent. The authors claimed that PRX-115 is a promising treatment option for gout and may offer the choice of a wide dosing interval.

PRX-115 is a recombinant homotetrameric uricase enzyme that catalyses the conversion of uric acid to allantoin, which is more soluble and easily excreted. PRX-115 is designed to have high specific activity, long half-life, and low immunogenicity. A phase 1, first-in-human, single ascending dose, double-blinded study (NCT05745727) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) following a single intravenous (IV) infusion of PRX-115, in 1 of 8 different dosages [1]. The study results were presented by Dr Orit Cohen Barak (Protalix BioTherapeutics, NJ, USA).

A total of 64 participants with gout were randomised to PRX-115 (n=48) or placebo (n=12); their mean age was 35 years, two-thirds were men, and mean urate levels were elevated (range 7.0–8.5 mg/dL). There were 8 cohorts, each with 6 participants on active treatment and 2 on placebo. Participants were followed for 12 weeks.

PRX-115 exposure increased in a dose-dependent manner, with maximal concentrations mainly observed directly after infusion. The higher dosages resulted in concentrations still quantifiable after 12 weeks. In all tested dosages, a single infusion of PRX-115 rapidly reduced plasma urate below 6.0 mg/dL. The urate-lowering effect and the duration of the response were dose-dependent, but urate concentrations remained below 6.0 mg/dL for 12 weeks with all dosages.

Dr Cohen Barak and colleagues found that PRX-115 was generally well-tolerated. The active groups had rates of treatment-emergent adverse events (TEAEs; 77%) similar to placebo (81%). Overall, 12 participants treated with PRX-115 reported 18 drug-related AEs, the majority of which were mild-to-moderate and transient. There was 1 serious AE, an anaphylactic reaction, which occurred immediately after PRX-115 was given (at a low dose). This event fully resolved, and the participant continued in the study. Following this incident, anti-histamine and steroid pre-medication was implemented; no other participants had a similar reaction.

1. Schwabe C, et al. Prolonged plasma urate-lowering after a single intravenous administration of PRX-115, a novel pegylated uricase, in participants with elevated urate levels. Abstract L05, ACR Convergence 2024, 14–19 November, Washington DC, USA.

Copyright ©2025 Medicom Medical Publishers



Posted on 13 January 2025