Cardiome Pharma Corp.'s stock held steady Thursday after the company reported that the FDA wants additional clinical and manufacturing data before it will approve oxypurinol for gout.
The company's stock (OTC BB:COMRF) fell 8 cents Thursday to close at $5.32.
Bob Rieder, president and CEO of Vancouver, British Columbia-based Cardiome, said the gout opportunity is "very small," adding that the company's main focus is on its cardiovascular drug development programs.
Nevertheless, the FDA issued an approvable letter on the oxypurinol (Oxyprim) application, which was submitted in December under accelerated approval guidelines. Oxypurinol has been declared an orphan product in gout (also called allopurinol-intolerant hyperuricemia).
The company said the FDA's letter warrants further investigation.
"We are not yet in the position to respond to the market because we have yet to internalize [the information]," Don Graham, Cardiome's director of corporate communications, told BioWorld Today.
Gout is a metabolic disorder caused by hyperuricemia (high serum uric acid levels) and results in the deposition of monosodium urate crystals in the tissues of the body, particularly in the joints and kidney. It is the most common cause of inflammatory arthritis in men older than 40, the company said.
Oxypurinol, the active metabolite of allopurinol, is a xanthine oxidase inhibitor. The drug has been used to treat allopurinol-intolerant patients since 1966 on a compassionate-need basis. Indeed, data on 533 patients in the compassionate-use program, as well as a 79-patient pivotal trial, which showed reductions in serum uric acid (SUA), made up Cardiome's new drug application. (See BioWorld Today, June 3, 2004.)
The pivotal study, referred to as OXPL213, demonstrated a highly statistically significant reduction in SUA (p<0.0001). However, it failed to achieve the primary endpoint of an average SUA decrease of 2 mg/dL between baseline and week 14. Overall, the mean decrease was 1.9 mg/dL, which the FDA previously has referred to as "clearly indicative of significant activity of oxypurinol."
Meanwhile, Cardiome is pushing forward with a 240-patient Phase IV study expected to take about two years. The primary efficacy analysis would consist of a comparison of the mean number of acute gout attacks vs. the oxypurinol and placebo groups.
In early June, Cardiome presented its gout data to the FDA's Arthritis Advisory Committee as part of a two-day discussion on trial design and endpoints for drug candidates for chronic and acute gout. The panel generally agreed that the reduction or elimination of acute attacks would be an appropriate primary endpoint for clinical trials.
Cardiome gained rights to oxypurinol from Paralex Inc., of New York, through a $20 million acquisition conducted in late 2001. Paralex, in turn, had gotten the drug from ILEX Oncology Inc., of San Antonio. (See BioWorld Today, Dec. 24, 2001.)
Elsewhere in the pipeline, Cardiome is developing an anti-arrhythmic product, RSD1235, as an acute-use, intravenous administration treatment for atrial fibrillation, a condition in which the atria of the heart beat rapidly and erratically. The intravenous candidate is in Phase III studies, while studies for the chronic oral therapy are expected to begin by the end of 2004.
Also, the company is studying oxypurinol in a Phase II trial for congestive heart failure.