Washington Editor

WASHINGTON – The FDA's approval late Tuesday of Savient Pharmaceuticals Inc.'s Krystexxa (pegloticase), a pegylated uric acid specific enzyme for chronic refractory gout, "symbolizes what a small biotech can do," said President Paul Hamelin.

The smallish East Brunswick, N.J.-based firm, which licensed Krystexxa's recombinant and manufacturing technology about a decade ago from Duke University and Mountain View Pharmaceuticals Inc., carried the drug through preclinical and clinical testing to U.S. approval without a development partner.

"What the 44 people in this company have done in the last few years is rather amazing, but that is the spirit of the biotech industry, and that is what's hopefully replicated in many companies across this country and in other areas as well," Hamelin told BioWorld Today. "It is the power of what people can do in today's world when we are bringing forward drugs that are not incremental improvements, but are dramatic improvements in medicine, and that just gets everybody so passionate. We are 44 overachievers."

Indeed, investors piggybacked on that enthusiasm Wednesday, driving shares of Savient (NASDAQ:SVNT) up 35.4 percent, or $5.22, to close at $19.98.

With Krystexxa's marketing in the U.S. assured – despite a few bumps along the way, including a complete response letter last year from the FDA – Savient has made no secret about its plans to sell the company. (See BioWorld Today, Aug. 4, 2009.)

Philip Yachmetz, senior vice president and general counsel, told investors and analysts Wednesday during a conference call that the decision to sell Savient, which was revealed in May in its first quarter report, came after a "careful and thorough evaluation of potential strategic alternatives," in which the company's board determined that such a plan was "the best way to realize the full global commercial potential of Krystexxa and would be the optimal outcome for the company's shareholders and other stakeholders."

Yachmetz said, however, that Savient could not comment further on its sales strategy because "it would be very detrimental to the company's efforts to have any public disclosure or discussion of the status or progress of this process or the likelihood or timing of the sales transaction, until such time as there is an announcement to be made for general public consumption."

Any information about a transaction, he added, must wait until a definitive agreement is executed.

But Hamelin emphasized that Savient plans, in parallel with its sales transaction, to pursue the launch of Krystexxa, which he noted is the "first-ever and only treatment" available in the U.S. for adults with chronic gout refractory to conventional therapy, by submitting promotional materials to the FDA's Division of Drug Marketing, Advertising and Communication, preparing and finalizing packaging and product distribution logistics and obtaining formulary reimbursement codes for public and private payers.

Savient's reasoning for pursuing the parallel strategy, Hamelin said, is because Krystexxa is a "medical breakthrough for the at least 170,000 crippled and disabled patients, who have no other therapeutic options.

"We feel very strongly that we owe these patients with chronic gout the opportunity to be in a position to initiate therapy as rapidly as possible, while we pursue our other corporate objectives," he said.

Hamelin noted that not all patients respond to currently marketed therapies for gout, such as xanthine oxidase inhibitors, like Zyloprim (allopurinol) and Uloric (febuxostat). Krystexxa, he insisted, addresses that "significant unmet medical need."

The efficacy and safety data supporting Krystexxa's approval was drawn from two multicenter, randomized, double-blind, placebo-controlled trials in patients with chronic gout refractory to conventional therapy. The primary efficacy endpoint was the proportion of patients who achieved plasma uric acid levels of less than 6 mg/dL for at least 80 percent of the time during month three and month six.

While the "medical wisdom" has been that if patients' uric acids could be lowered to even slightly below 6 mg/dL, "then it was presumed that new deposits of urate crystals would slow," Hamelin said. But within hours of the first infusion of Krystexxa, he said many patients achieved a lowering of their serum uric acid level from a baseline mean of about 10 mg/dL to a mean of 0.7 mg/dL – or "five times lower than what these chronic gout patients can experience with existing conventional therapy."

Those patients also achieved a complete response for the resolution of tophi within the first six months of therapy, Hamelin added. That "powerful and sustained" lowering of the uric acid, he said, "leads to the clinically meaningful change in the disease.

"For the first time, these patients will have a new therapeutic treatment option, which provides them with unique clinically and medically meaningful benefits within six months of treatment commencement – something that has never been achieved before in this patient population," he said.

Hamelin noted that Savient has agreed to conduct a post-approval observational registry trial of Krystexxa, which is an intravenous therapy administered once every two weeks, in 500 patients over one year to further evaluate the identification of any serious adverse events, including infusion reactions and anaphylaxis.

Barry Quart, CEO of Ardea Biosciences Inc. – a potential future competitor in the gout space – praised Krystexxa's approval as a win for all biotech developers of gout medications and patients.

He noted that Ardea's drug, RDEA594, a selective URAT1 transporter inhibitor, has a different mechanism of action than Krystexxa and "works on the mechanism that 90 percent of patients have the defect in that causes the gout."

Quart said RDEA594, which is expected to enter Phase III testing next year, works "extremely well with contemporary therapy." Recently reported Phase IIb monotherapy results showed that Ardea's drug had a 60 percent response rate in 123 gout patients.

Although Krystexxa has a head start in the marketplace, Quart said Savient's drug is intended for a specific population and is an IV drug, whereas RDEA594 is an easier-to-use oral therapy aimed at a larger population. But, he added, Krystexxa's approval is "very exciting" for all gout drugmakers.

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