The FDA has approved the first fixed-dose combination treatment designed to address in a single pill both causes of hyperuricemia in gout—overproduction and underexcretion of serum uric acid.

Ironwood Pharmaceuticals will market Duzallo® (lesinurad and allopurinol), which is indicated as a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone.

Allopurinol is a xanthine oxidase inhibitor (XOI) whose action differs from that of uricosuric agents such as lesinurad. Allopurinol is designed to reduce the production of uric acid (UA); while lesinurad is designed to increase renal excretion of UA by selectively inhibiting the action of URAT1, the UA transporter responsible for most renal UA reabsorption.

Duzallo will be available in dosages that combine 200 mg of lesinurad with 300 mg of allopurinol, as well as 200 mg of lesinurad plus 200 mg of allopurinol. Duzallo will be marketed with a boxed warning regarding the risk of acute renal failure, Ironwood said.

“With Duzallo, nearly twice as many patients with uncontrolled gout may be able to achieve target sUAlevels compared to those patients taking allopurinol alone, which is important, considering the significant unmet need among uncontrolled gout patients to get to goal of under 6 mg/dL,” Tom McCourt, Ironwood’s svp of marketing and sales and chief commercial officer, said in a statement.

McCourt added that Ironwood expects Duzallo to serve as a “critical driver” of its gout franchise, which is expected to exceed total annual U.S. peak sales of $300 million.

Ironwood reported approximately $100,000 in net sales for Zurampic® last year, based on 371 total prescriptions filled in the fourth quarter—and $800,000 in net sales in the first half of this year, based on approximately 2400 total prescriptions—with Q2 alone generating $500,000 in net sales and 1500 prescriptions.

Part of Up-to-$265M Deal

Ironwood acquired U.S. rights to Duzallo last year when it licensed exclusive U.S. rights from AstraZeneca to all products containing lesinurad—including the gout-associated hyperuricemia drug Zurampic, which was launched in October 2016. In return for those rights, Ironwood agreed to pay AstraZeneca $100 million upfront and up to $165 million in payments tied to sales and other unspecified milestones, as well as tiered single-digit royalties on product sales.

An AstraZeneca subsidiary, Ardea Biosciences, submitted the Duzallo New Drug Application (NDA) to the FDA. The NDA was based on data from two Phase III trials CLEAR 1 (n=402) and CLEAR 2 (n=410), whose results showed the efficacy and safety of lesinurad plus allopurinol—as well as 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.

In clinical trials of adults with gout who failed to achieve target sUA levels using allopurinol alone, lesinurad plus allopurinol nearly doubled the number of patients who achieved sUA target of <6 mg/dL at month 6, reduced the mean sUA level to <6 mg/dL by month 1 and maintained that level through month 12.

The most common adverse reactions in clinical trials were headache, influenza, higher levels of blood creatinine, and acid reflux, Ironwood said.

Duzallo is not recommended for the treatment of asymptomatic hyperuricemia.

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