PRX-115 promising treatment option for patients with gout, finds study

A recent study presented by Orit Cohen Barak in the ACR Convergence 2024 showed that with the extra advantage of a potentially broad dose interval, PRX-115 (Protalix BioTherapeutics) may provide an efficient urate-lowering medication that might improve patient compliance and treatment flexibility of gout cases.

PEGylated uricases have previously shown promise as a therapeutic approach for treating individuals with refractory gout. Utilizing a novel plant cell-based expression technique, the recombinant homotetrameric uricase enzyme PRX-115 is generated from Candida utilis. After purification, the enzyme undergoes a unique modification using unique polyethylene glycol (PEG) molecules. High specific activity, enhanced stability, and decreased immunogenic potential are all features of PRX-115's design.

A single intravenous (IV) infusion of PRX-115 was used to evaluate its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in a first-in-human single ascending dosage, double-blinded research (FIH-SAD, NCT05745727). A total of 64 participants, the majority of whom had high urate levels (>6.0 mg/dL), were recruited for the trial and randomly assigned to either PRX-115 or a placebo in a 3:1 ratio (8 cohorts; 6 participants on active and 2 on placebo each cohort). The participants were monitored for 12 weeks, or 85 days. 

The findings suggest that PRX-115 single ascending dosages were usually well tolerated, according to key findings from the first 7 cohorts. A total of 18 associated Treatment Emergent Adverse Events (TEAEs) were reported by 11 (26%) subjects who received PRX-115; most of them were mild to moderate and temporary in character. At a modest dosage, one significant adverse event (SAE, anaphylactic response) happened right after the infusion started. The person persisted in the trial when the SAE had completely resolved.

Exposure to PRX-115 grew in a dose-dependent manner, with detectable amounts up to 85 days (12 weeks) after treatment at the high dosages and peak concentrations being recorded right after infusion. A single dosage of PRX-115 quickly lowered plasma urate below 6.0 mg/dL in all tested doses. With urate levels below 6.0 mg/dL that persisted for 12 weeks, the urate-lowering efficacy and response duration were dose-dependent.

Overall, the findings of this FIH-SAD study's first seven cohorts show that PRX-115 may be able to provide a broad dose interval and is a potentially effective therapy choice for gout patients. To validate these results and determine PRX-115's long-term safety and effectiveness in gout patients, more research is necessary.

Source:

Prolonged plasma urate-lowering after a single intravenous administration of PRX-115, a novel PEGylated uricase, in participants with elevated urate levels. (2024, October 15). ACR Meeting Abstracts. https://acrabstracts.org/abstract/prolonged-plasma-urate-lowering-after-a-single-intravenous-administration-of-prx-115-a-novel-pegylated-uricase-in-participants-with-elevated-urate-levels/