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FDA Approves New Drug for Gout

The FDA has approved lesinurad (Zurampic) ­­– to be used in combination with allopurinol (Zyloprim) or febuxostat (Uloric) — for the treatment of hyperuricemia associated with gout. Lesiunard is the first in a new class of drugs called selective uric acid reabsorption inhibitors (SURIs) to be approved in the United States.

It represents an important advance in treatment for people whose gout is not controlled by current medications, says Jasvinder Singh, MD, a rheumatologist at the University of Alabama at Birmingham (UAB) and one of the investigators in the clinical trials on which the approval of lesinurad is based. Gout is a painful and potentially debilitating form of inflammatory arthritis that affects up to 4 percent of American adults.

Lesinurad works in a novel way to lower blood levels of uric acid, a bodily waste product responsible for gout. When uric acid reaches high levels in the blood (hyperuricemia), the acid can leak out and deposit as crystals in the joints and other tissues, resulting in intense pain and swelling. Early in the disease course, gout attacks usually occur in one joint, often the big toe. Repeated attacks, or flares, can lead to irreparable damage of the affected joint(s) as well as interfere with a person’s quality of life and work productivity, says Dr. Singh, who is also a professor at UAB’s division of clinical immunology and rheumatology.

Acute gout attacks are treated with anti-inflammatory medications; however, drugs to lower uric acid are needed to prevent or lessen the frequency of subsequent attacks. Unlike most current gout medications, which decrease the body’s production of uric acid, lesinurad increases its excretion. The drug works by inhibiting a protein called urate transporter 1 (URAT1), which is responsible for the majority of uric acid reabsorption by the kidneys. This difference, says Dr. Singh, makes it possible to combine lesinurad with existing drugs, such as allopurinol or febuxostat – both known as xanthine oxidase inhibitors, or XOIs – to enhance the effects for people whose gout is not controlled by XOIs alone.

“A different mechanism is always something that allows us to combine drugs without having a similar side effect or toxicity profile,” says Dr. Singh. “It gives us more of an option. It also helps us understand the disease better, not only how to treat it better now, but it probably leads to more discovery down the path,” he says.

In two phase III studies, a significantly larger percentage of patients taking lesinurad (either 200 mg or 400 mg doses) along with allopurinol achieved target serum uric acid levels – below 6.0 mg/dL – at six months compared to those taking allopurinol alone. “The target is important because studies have shown that the target correlates very well with number of flares, with costs, with productivity loss, with how people are doing with the disease,” says Dr. Singh. “That level has a meaning, and keeping below that level allows people to function much more normally.”

At 200 mg doses (the dose approved by the FDA), lesinurad compared favorably in safety to allopurinol alone, with a couple of exceptions, says Dr. Singh. The group taking lesinurad with allopurinol had worse numbers in a test that measures kidney function, which was reversible, and an increased risk of cardiovascular events.

The FDA is requiring the drug maker to continue to evaluate the kidney and cardiovascular safety of lesinurad in a postmarketing study. Dr. Singh says he also hopes to see studies of the drug in different populations to determine if more people can benefit from it. For now, he says, lesinurad is an important addition for people whose gout is not controlled by allopurinol alone.

Donald Miller, PharmD, professor in the department of pharmacy practice at North Dakota State University, agrees. “Lesinurad will offer gout patients an important new option to obtain better control of the condition,” says Miller, a member of the FDA Arthritis Advisory Committee, which in October voted 10-4 to recommend the approval of lesinurad in combination with an XOI for the treatment of hyperuricemia associated with gout. “It is not a first line therapy, but can be added to allopurinol or febuxostat when those drugs alone do not control high blood levels of uric acid. However, it will be important for patients to be aware of the precautions that should be taken, such as staying well hydrated to avoid formation of kidney stones.”

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