In 2005, results from our Phase 2 Puricase clinical trial underscored the promise of our innovative strategy for combating the underlying biochemical imbalances that cause gout and its painful symptoms. Gout occurs when uric acid levels rise above the biochemical limit of solubility, precipitates, and accumulates in and around joints and in other tissues in the form of needle-like urate crystals. Pain and swelling, and erosion of cartilage and bone, are thought to result from the body’s exaggerated immune response to these abnormal crystal deposits. Evidence suggests that the chronic elevations of uric acid associated with gout may also have systemic consequences, including increased risk for hypertension and kidney disease. Research has focused on the reduction of circulating uric acid as a key pathway for effective treatment. However, new approaches for normalizing uric acid levels and eliminating urate crystals from the tissues may be important for addressing the needs of gout sufferers.
Puricase is a recombinant, pegylated formulation of porcine urate oxidase, an enzyme present in almost all mammals – but not in humans – that lowers uric acid levels in the blood. Our Phase 2 trials demonstrated that Puricase delivered substantial and sustained reduction of elevated plasma urate levels in treated patients.
Our Phase 3 protocol, as approved by the FDA in a special protocol assessment, will measure the association between Puricase-induced reductions in plasma urate in gout sufferers. The effect of the drug on potential clinical outcomes will also be assessed and will include:
- Elimination of gout tophi (as demonstrated by digital photography, image analysis central reading)
- Reduction in frequency of gout flares
- Improvement in the count of swollen and tender joints
- Overall improvement in patient-reported outcomes.
Enrollment in the placebo-controlled, 6 month clinical trials will include approximately 200 patients in the United States, Canada and Mexico, all of whom have failed other attempts to normalize uric acid levels. The primary efficacy measurement will be an assessment of the proportion of patients with normalized uric acid levels on treatment as compared to placebo. Clinical efficacy, together with an acceptable safety profile, will demonstrate the benefit of the novel therapeutic approach with Puricase.
The first patient dosing occurred in June 2006, with patient enrollment completed in March 2007. A Biologics License Application (BLA) submission is anticipated in early 2008.
We’re excited about the critical next steps in Puricase development and look forward to a successful entry into the rheumatology marketplace in 2009 with a true innovation that resolves a fundamental and elusive problem facing patients living with unrelenting pain.
The following abstract titles were selected for poster presentations at the European League Against Rheumatism (EULAR) 2006 Annual Meeting:
- "A Multicenter Longitudinal Study of Disease Characteristics in Patients with Treatment-Failure Gout"
- "Quality of Life in Patients with Treatment-Failure Gout"
- "A Phase 2 Study of Multiple Doses of Intravenous Polyethylene Glycol (PEG)-uricase in Patients with Hyperuricemia and Treatment-Failure Gout"
- "Resolution of Tophi with Intravenous PEG-uricase in Treatment-Failure Gout"
To view chosen abstracts, please visit the congress website at: www.eular.org/eular2006.
If you are a patient or a physician wishing to learn more about the Phase 3 protocols, please use the following links:
If you believe you or your patient might be eligible for participation, please call our patient recruitment service number: 1-866-304-3060.