FDA Febuxostat Review Could Boost Savient Gout Agent

FDA's convening of a November advisory committee on Takeda North America's febuxostat for treatment-failure gout may give a boost to Savient's Puricase , which could be used as an induction agent and may get its own panel review.

The agency announced the meeting of the Arthritis Drugs Advisory Committee on Oct. 14.

If the agency follows the six-month review cycle for febuxostat, approval could come in March. This is another possible upside for Savient, since a prospective maintenance therapy would already be in place and regulators would not need to be concerned about TFG patients who quit Puricase and relapse.

"It's unknown right now" how long patients would stay on Puricase, said Paul Hamelin, Savient's senior VP of commercial operations. "There are a lot of theories we could all postulate."

Ninety-two percent to 98 percent of gout patients on chronic therapy get allopurinol, the xanthine oxidase inhibitor approved in 1964, but 10 percent prove allergic to the drug or have severe adverse events. This is the orphan population targeted by both febuxostat and Puricase, a recombinant, pegylated formulation of modified mammalian urate oxidase. Both work similarly to allopurinol.

Savient plans to file the BLA for Puricase in TFG by the end of this month. Puricase is "literally removing the body's total burden of urate crystals, so we're seeing changes in the clinical picture of the disease," Hamelin said. "[Patients] become flare free, tophi free, and then could go back to some level of treatment."

Investors clipped the firm's shares by 15 percent in late September, after CEO Christopher Clement said Savient had not yet signed a partner for the product and was exploring "all potential options." The advisory committee news restarted takeover speculation that began in the spring, when Puricase yielded positive Phase III results (¹ (Also see "Savient: Still No Partner For Gout Drug" - Pink Sheet, 26 Sep, 2008.)).

"We've never been in a hurry to partner this product," Hamelin said, noting that Savient has enough cash to take the drug through the BLA filing and launch alone. He pointed to "value creation step-ups" coming soon, such as the filing and six abstracts being presented in late October at the American College of Rheumatology meeting, where Savient is expected to unveil full Phase III results.

Meanwhile, Takeda North America is preparing for the febuxostat meeting on Nov. 24. Takeda and Abbott developed the oral, once-daily drug for management of hyperuricemia in patients with chronic gout. Takeda took control of the compound, along with heartburn and GERD drug Prevacid (lansoprazole), in the takeover of TAP Pharmaceuticals, its joint venture with Abbott, earlier this year (² (Also see "Takeda Buys Abbott’s Stake In TAP Joint Venture" - Pink Sheet, 19 Mar, 2008.)).

Febuxostat's approval road has been rocky. Lake Forest, Ill.-based TAP received an approvable letter from FDA in August 2006 for its febuxostat NDA, after getting an initial approvable letter the previous October. At the time, the company said it would ask for clarification from FDA, but concerns listed in the FDA letters have not been publicly disclosed.

Japan's Teijin Pharma and its European partner gained marketing clearance from the European Commission for the drug in May. The firms plan to launch the drug in Europe as Adenuric . Takeda hopes to market the product as Uloric in the U.S.

Leerink Swann analyst Joseph P. Schwartz, in an Oct. 7 research note, praised Puricase's "elegant mechanism of action, ... unprecedented efficacy," and lack of safety concerns. He modeled revenues of $750 million in 2015, counting only a 0.9 percent penetration into the gout patients who get urate-lowering therapy. Schwartz "conservatively" estimated a cost of $30,000 per year for Puricase.

Also at the upcoming ACR meeting, Savient will offer data showing that gout, long considered less debilitating than rheumatoid arthritis, is just as serious, Hamelin said, noting that other firms are climbing aboard the gout bandwagon with earlier stage research.

Among them is Ardea Biosciences. Developing a potential HIV therapy, the firm discovered that the drug lowered uric-acid levels in some patients. In August, UK regulators authorized a Phase I study evaluating oral RDEA594 for gout.

Eyes, though, are mostly on febuxostat and Puricase for gout, the most severe form of which strikes older males, often after "chronic low level inflammation going on for years," even affecting the kidneys, Hamelin said. How the treatment landscape will evolve with the pair of therapies is uncertain, but there's no question about need. "Everyone is searching for new therapeutic options here," Hamelin said. "We hope both drugs get approved."

- Randall Osborne ([email protected])