Washington Editor

Shares of Ardea Biosciences Inc. gained 12.3 percent Thursday after the company said its Phase IIb dose-escalation study of RDEA594, a selective URAT1 transporter inhibitor, met its primary endpoint of significantly reducing serum urate levels in patients with gout after four weeks of treatment vs. placebo.

The San Diego-based biotech's shares (NASDAQ:RDEA) had climbed as much as 30 percent earlier in the day Thursday, before closing at $20.50, a gain of $2.24.

Ardea CEO Barry Quart noted that the data, which the company reported shortly after the markets closed Wednesday, were preliminary top-line results. "We had rushed to get this top-line data out as quickly as possible," he told investors and analysts during a conference call.

"It will take several more months for the study to be fully analyzed," Quart said, adding that the firm plans to present full details at a future scientific conference.

Nonetheless, the strong data reported Wednesday evening should strengthen Ardea's potential for partnership negotiations on the compound, said Leerink Swann analyst Joseph Schwartz. He predicted that a deal could come shortly after Ardea reports data from its Phase IIb trial of RDEA594 in combination with allopurinol - the mainstay treatment for gout - with those results expected in the second quarter.

Quart said one of Ardea's "primary targets" is to identify a potential regional partnership in Japan, where patients tend to get treated on a much earlier time frame. "With these data, we now have the opportunity to push that process forward," he said. "We do believe that we have keen interest amongst many companies, and we believe that the data that have been generated in this study will go a very long way toward enhancing that interest, particularly on a regional basis," Quart said.

Once Ardea has the Phase IIb data from both studies in hand, Quart said his firm plans to meet with the FDA to discuss Phase III clinical development of RDEA594.

Ardea's positive results came the same week that East Brunswick, N.J-based Savient Pharmaceuticals Inc. announced the FDA accepted its application resubmission for the firm's gout drug Krystexxa (pegloticase),

Savient, which had hoped to be the second firm in 45 years to enter the gout market after the February 2009 approval of Takeda Pharmaceutical Co. Ltd.'s Uloric (febuxostat), had received a complete response letter last August from the FDA for Krystexxa. (See BioWorld Today, Aug. 4, 2009.)

For Ardea's study, Quart said 123 gout patients with hyperuricemia received once-daily dosages of RDEA594 at 200 mg, 400 mg or 600 mg or placebo in the 28-day, randomized, double-blind, placebo-controlled, dose-escalation Phase IIb study.

Patients receiving the once-daily 400-mg and 600-mg dosages of RDEA594 had their dose titrated up weekly in increments of 200 mg per day, he said.

Quart noted that the trial specifically enrolled so-called underexcretors - patients who excrete less than normal amounts of uric acid at baseline - which make up about 90 percent of all gout patients.

He emphasized that all patients received colchicine as a prophylaxis against flare-ups.

The primary endpoint was a significant increase in the proportion of patients who achieved a reduction of serum urate to less than 6 mg/dL after four weeks of treatment vs. placebo.

Quart said reductions in serum urate and response rates increased in a dose-related manner and were "highly clinically and statistically significant" at both the 400-mg and 600-mg once-daily dosages.

At the highest dose, there was a 38 percent median reduction in serum urate levels after four weeks of treatment, compared with a 1 percent increase on placebo, which Quart said translated into a response rate of 45 percent in the treatment group.

He noted that the Phase IIb dose-escalation study enrolled patients who had a median 9.8 mg/dL baseline serum urate level, which Quart said was higher than those observed in Ardea's previous studies.

The response rate at the highest dosage in patients with baseline serum urate levels of less 10 mg/dL was 58 percent, with a "p" value of 0.0012.

Quart noted that patients with serum urate levels below 10 mg/dL make up about 95 percent of the gout patients in clinical practice.

"So certainly looking at this subset is very clinically relevant," he told investors and analysts.

Quart said RDEA594 was well tolerated in the Phase IIb trial, with no serious adverse events reported. There also was no difference in the rate of adverse events considered to be at least possibly related to treatment between the groups receiving RDEA594 and placebo, he added.

Quart acknowledged, however, that two patients, or 2 percent of the treatment group, discontinued the study due to an adverse event determined to be related to RDEA594.

One patient discontinued due to vertigo, while another dropped out because of a "transient increase" in serum creatinine, which Quart noted returned to normal levels before the patient discontinued the drug.

He acknowledged that a "small number" of transient increases in serum creatinine were observed during the screening period before administration of drug and during the randomized portion of the study.

There were three patients who experienced grade 1-2 increases in serum creatinine lasting for two or more weeks, but Quart noted that one of those patients already had a grade 1 elevation at baseline.

He also pointed out that serum creatinine levels in the other two patients treated with RDEA594 "returned to within normal limits" after completing the treatment period. "There was no dose relationship to these events," Quart emphasized.

Almost all increases in serum creatinine, both pretreatment and during the dosing period, were observed in patients with high baseline serum urate levels. "These patients are known to be at higher risk for renal dysfunction," Quart said.

Leerink's Schwartz said that, in his view, RDEA594's safety profile "exceeded cautious expectations and alleviates concerns."

Cowen & Co. analyst Phil Nadeau agreed, calling the safety data "encouraging," stating that they compare "quite favorably" with currently approved therapies.