06/16/09 A panel of experts has recommended that the Food and Drug Administration approve a new therapy intended to help people with severe gout who have failed treatment on other kinds of drugs.
The panel, a mix of rheumatologists, cardiologists, statisticians and consumer and patient advocates voted 14-1 to recommend approval of pegloticase (Krystexxa), an orphan drug developed by Duke University and Mountain View Pharmaceuticals and licensed by Savient Pharmaceuticals.
If the FDA approves pegloticase, it will be the first treatment of its kind for gout and only the second new drug approved to treat the painful joint disorder in 40 years. The agency is not bound by the advisory committee’s vote but usually follows it.
As Americans gain weight, doctors are seeing a sharp rise in the number of cases of gout, a painful condition caused by an excess of a metabolic by-product called uric acid. When uric acid builds, it can form needle-like crystals that deposit in the joints and other organs, causing severe pain, inflammation, and hard lumps called tophi.
An estimated 100,000 people in the United States with gout cannot tolerate or do not respond to existing treatments. They may develop a chronic form of the condition, which can cause erosion of the joints and severe disability.
In an attempt to help this population, the FDA gave the drug orphan drug status, a designation that offers tax incentives to companies that develop drugs to help relatively small numbers of people, and fast-tracked its review.
Unlike other medications for gout, which work by blocking the formation of uric acid or by increasing the rate of its removal from the body, pegloticase is an enzyme that breaks down uric acid so it can be excreted.
In the clinical studies reviewed by the panel, study participants who took eight milligrams of pegloticase by infusion every two weeks for six months had significantly lower levels of uric acid, a significant reduction in the number of swollen and tender joints and tophi, and had significantly fewer flares when compared to those on a placebo. Participants who took eight milligrams every four weeks for six months also saw an improvement in their symptoms compared to a placebo, though it was not as great as with the more frequent dosing.
Before the Arthritis Advisory Committee met on Tuesday, the FDA released briefing documents that indicated that regulators were convinced that pegloticase was effective, but that they were worried about drug’s safety.
Notably, A greater proportion of patients who got the experimental treatment experienced serious cardiac events, including heart failure and heart attacks, than those who were on the placebo. Study participants in the pegloticase group also had a greater number of infusion and allergic reactions than those on the placebo, and they were also more likely to develop an immune response to the drug that prevented it from working.
Because the studies were small, the panel of experts was asked by regulators to determine if the adverse events reported by the company that’s developing the drug represented a “genuine safety signal” or if they could be attributed to the underlying disease process. A buildup of uric acid in the body is associated with a greater risk for cardiovascular disease.
The committee concluded that though questions of safety remain, the dramatic improvements seen in about half of patients who took the drug outweighed its risks.
