Gout, a debilitating form of arthritis, has historically been referred to as "the disease of kings," afflicting rich old men who eat and drink too much. In fact, scientists say it is unclear why some people develop gout and others do not, although there is some evidence that the disease has both genetic and lifestyle underpinnings.
The disease occurs when there is so much uric acid in the blood that the body can't get rid of it quickly enough. The excess precipitates into crystals that clump in and around joints and tendons, triggering inflammation. It can spread from there. Affected areas become red, swollen, and painful. In extreme cases, gout can leave patients unable to walk or handle basic tasks like tying shoes or handling a knife or fork.
Two to three million people in the U.S. suffer from gout. "The typical patient is male, probably in his forties or fifties, who suddenly develops searing pain in one of his big toes," says John Sundy, a rheumatologist and associate professor of medicine at Duke.
Sundy is the lead investigator on one of two Phase III clinical trial studies for a new drug, pegloticase, that inventors say reduces excess uric acid more quickly and efficiently than existing treatments by breaking it into products the body can more easily eliminate.
"There hasn't been a new drug for gout in the U.S. for over forty years," Sundy says. "While most gout patients do well with the drug allopurinol, there is a subset of about 50,000 patients in the U.S. who don't respond to it or who can't tolerate it and who have no real alternatives."
The results of the Phase III trials, which enrolled a total of 212 patients, have so far been mixed. Each patient received eight milligrams of pegloticase or a placebo every two or four weeks for six months. Researchers measured uric acid levels and crystal deposits over time.
They found that uric acid levels fell to target levels among all patients within six hours after receiving the medication and remained at target levels in about 40 percent of patients when measured three and six months later. There was also a significant reduction of the size and number of deposits among those patients getting pegloticase, compared with those getting a placebo.
However, almost all of the patients experienced some side effects, and thirty-two withdrew from the studies because of them.
Pegloticase, a manufactured enzyme, was created by Michael Hershfield, a professor of medicine and biochemistry at Duke; Susan Kelly, a researcher in Hershfield's lab; and scientists at Mountain View Pharmaceuticals. The drug is developed and produced by Savient Pharmaceuticals Inc., which sponsored the studies.
January 31, 2009