Ironwood Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) for DUZALLO (fixed-dose combination of lesinurad and allopurinol) for the treatment of hyperuricemia in patients with uncontrolled gout. The FDA Prescription Drug User Fee Act (PDUFA) target action date is expected to occur in the second half of 2017 and, if approved, DUZALLO is expected to be commercially available in late 2017. It is estimated that approximately half of the four million gout patients in the U.S. treated with a xanthine oxidase inhibitor (XOI), either allopurinol or febuxostat, are uncontrolled and are not achieving target serum uric acid (sUA) levels <6 mg/dL as recommended by the American College of Rheumatology. Lesinurad is currently approved by the FDA under the brand name ZURAMPIC® to be taken in combination with an XOI for the treatment of hyperuricemia – high levels of uric acid in the blood – associated with gout in patients who have not achieved target sUA levels with an XOI alone. ZURAMPIC is not recommended for the treatment of asymptomatic hyperuricemia and should not be used as monotherapy. Lesinurad is a once-daily oral tablet that lowers sUA by reducing reabsorption of uric acid, thereby increasing renal excretion of uric acid. The mechanism of lesinurad is distinct from and complementary to that of an XOI, which reduces production of uric acid. Together, the dual-mechanism combination of lesinurad plus an XOI can address both inefficient excretion and overproduction of uric acid. Currently, patients with uncontrolled gout are often treated with higher doses of XOIs that may require multiple pills daily in an attempt to reach their sUA target. If approved, DUZALLO would be the first treatment to offer this dual-mechanism of action in a single pill to be taken once per day. The NDA for DUZALLO is based on the extensive clinical program supporting the ZURAMPIC NDA and a pharmacokinetic study that evaluated the bioequivalence of the fixed-dose combination of lesinurad and allopurinol compared to co-administration of separate lesinurad and allopurinol tablets. The efficacy and safety of the two drugs co-administered separately was demonstrated in two pivotal Phase III clinical trials, CLEAR 1 and CLEAR 2, which supported the ZURAMPIC NDA. In these clinical trials in adult patients with gout who failed to achieve target sUA levels on allopurinol alone, the addition of ZURAMPIC nearly doubled the number of patients who achieved sUA target of <6 mg/dL at month 6, reduced the mean sUA to <6 mg/dL by month 1 and maintained that level through month 12. Acute renal failure has occurred with ZURAMPIC and was more common when ZURAMPIC was given alone. The most common adverse reactions with ZURAMPIC in the clinical trials were headache, influenza, blood creatinine increased, and gastroesophageal reflux disease. The DUZALLO NDA was submitted by Ardea BioSciences on behalf of Ironwood.