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Gout: The most common inflammatory arthritis in the United States

Affects an estimated 14  million adults in the United States.

An estimated approximately 5% of the gout population is considered to have chronic refractory disease. Patients with other severe forms of gout may also benefit from new therapies.

Uncontrolled Gout

Cause

Uncontrolled gout occurs when urate-lowering therapies (ULTs therapies fail to lower serum uric acid (sUA) levels below the gout guideline goal of 6 mg/dL at the maximum medically appropriate dosage or when gout does not improve clinically with oral urate-lowering therapies (ULTs), and may involve systemic urate deposition. Uncontrolled gout is also reported to involve urate crystal deposition and associated inflammation in joints, soft tissues, and organs, such as the heart, kidneys, and eyes. Currently available ULTs can be effective in treating gout. However, low adherence, under dosing and disease progression that cause high patient burden. We believe that new, effective and safe therapies to treat these underserved uncontrolled gout patients.

Uncontrolled Gout

The risk of gout increases with age, and it is thus more common in ageing populations. Gout results from sustained elevation of serum urate levels (hyperuricaemia). Urate levels may increase due to diet, genetic predisposition and environmental factors leading to the deposition of monosodium urate crystals, which triggers recurrent episodes of pronounced acute inflammation, known as gout flares. Gout leads to substantial morbidity, severe pain, reduced quality of life, decreased physical function, increased healthcare costs, and lost economic productivity. In some patients a conglomerate of inflammatory cells and monosodium urate form Tophi, which can form on joints, tendons and other soft tissue, which can cause pain and deformation. Furthermore, gout is strongly associated with a number of comorbidities, including hypertension, cardiovascular disease, renal impairment, diabetes, obesity, hyperlipidaemia and frequently in a combination known as the metabolic syndrome.

cause

PRX-115

A Recombinant PEGylated uricase enzyme,   Chemically modified enzyme in development for the potential treatment of severe gout.
PRX-115 is our recombinant PEGylated uricase (urate oxidase) – a chemically modified enzyme under development for the potential treatment of patients with uncontrolled gout. The uricase enzyme converts uric acid to allantoin, which is easily eliminated through urine and does not exist naturally in humans. This recombinant enzyme, expressed via our ProCellEx system, is designed to lower uric acid levels and improve clinical manifestation of the disease while having low immunogenicity and increased half-life of the drug in the blood.

Pre-clinical data demonstrates long half-life, reduced immunogenic risk and high specific activity which supports the potential of PRX-115 to be a safe and effective treatment for patients with gout. One-month multiple dosing toxicity studies in two species and 6-month multiple dosing toxicity study in one species were conducted to support single and multiple dose studies is humans.

Clinical Development

PRX-115 is being studied in a phase I First in Human single ascending dose clinical trial to evaluate its safety, pharmacokinetics, pharmacodynamics and immunogenicity in patients with elevated uric acid levels.

It is  a double blind, placebo-controlled study where 56 randomized subjects  were enrolled across seven cohorts, 42 subjects were treated with PRX–115 and 14 subjects were treated with a placebo.

Key preliminary results are as follows:

Exposure to PRX–115 increased in a dose–dependent manner

PRX–115 rapidly reduced plasma uric acid concentrations to below 6.0 mg/dL over time following a single administration. The effect of PRX–115 on plasma uric acid concentrations and the duration of response was found to be dose dependent

PRX–115 was well-tolerated

After a review of the initial positive top–line results from the seven cohorts, and The FIH Study is being expanded to an additional cohort to analyze a higher dose and preparations for a phase II clinical trial of PRX-115 have commenced.