FDA Approves Zurampic for Gout
The U.S. Food and Drug Administration has approved a new treatment for gout. When used in combination with a xanthine oxidase inhibitor (XOI), Zurampic (lesinurad) helps to reduce the high levels of uric acid (hyperuricemia) that is associated with gout, noted a press release from the agency.1
"Controlling hyperuricemia is critical to the long-term treatment of gout," said Badrul Chowdhury, MD, director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. "Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes."
Gout is now the most common inflammatory arthropathy in the United States,2 where it is estimated to affect more than 8 million people, or 3.9% of adults.
"Gout is a common ailment, and therapy can be tricky, so new treatment options are always welcome," commented Douglas White, MD, PhD, Chair, Committee on Rheumatology Care for the American College of Rheumatology (ACR) to Practical Pain Management.
"That said, there have been some safety concerns about this medicine based on adverse events in the clinical trials when it was used at doses higher than 200 mg per day or when it was used without an XOI," noted Dr. White. "So, as with all new drugs, post-marketing surveillance will be important to make sure it doesn't pose undue risk to patients," he said.
Gout presents as an acute mono- to poly-articular joint inflammation. Severe pain, redness, and swelling occur along with the potential for serum leukocytosis, low-grade fever, and elevated blood inflammatory markers,3 according to Robert T. Keenan, MD, MPH, Assistant Professor of Medicine, Division of Rheumatology and Immunology, at Duke University School of Medicine, in Durham, NC.
Most people with hyperuricemia do not develop gout, but if uric acid forms crystals in the body, gout can develop. According to the manufacturer, AstraZeneca, "Zurampic inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. By inhibiting URAT1, Zurampic increases uric acid excretion and thereby lowers serum uric acid."4
Responding to the increasing prevalence of gout, as well as to new therapies based on improved understanding of gout pathophysiology, the ACR developed non-pharmacologic and pharmacologic treatment recommendations for both acute and chronic gout in 2012.5,6
At the time, the ACR guidelines did not address the future role of urate-lowering therapy in development, such as ulodesine, lesinurad, and tranilast.
Zurampic joins four FDA-approved medications to lower uric acid levels. Allopurinol and febuxostat (Uloric) are XOI that prevent the body from making urate by inhibiting xanthine oxidase, while probenecid (Probalan) and pegloticase (Krystexxa) help the body eliminate urate via the kidneys and metabolizing urate, respectively.
How it Was Approved
The safety and efficacy for Zurampic were evaluated in Phase III studies, CLEAR1, CLEAR2 and CRYSTAL, involving 1,537 patients who were also given a XOI for up to 12 months. According to the study results, the patients treated with Zurampic in combination with a XOI experienced reduced serum uric acid levels compared to controls who received placebo.
The most common adverse reactions in clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease.
Zurampic has a boxed warning that provides important safety information for health care professionals, including the risk for acute kidney (renal) failure, which is more common when used without an XOI and with higher than approved doses of Zurampic.
The FDA is also requiring a postmarketing study to further evaluate the renal and cardiovascular safety of Zurampic.
Zurampic is manufactured by AstraZeneca Pharmaceuticals LP, based in Wilmington, Delaware.