The race for a new generation of chronic gout treatments is on, but the contest may not be a case of winner takes all.

Two gout drugs, Savient Pharmaceuticals Inc.'s Krystexxa (pegloticase) and Takeda Pharmaceutical Co. Ltd.'s Uloric (febuxostat), were approved in the last few years, but BioCryst Pharmaceuticals Inc. and Ardea Biosciences Inc. see more opportunities in the growing market.

Krystexxa is a biologic approved to treat refractory chronic gout, so there's room for drugs to slip in ahead of it in the treatment paradigm. And Uloric works the same way as an older generic, allopurinol, so drugs used in combination with allopurinol should also work with Uloric.

Last week, BioCryst presented Phase IIb data for BCX4208 at the American College of Rheumatology and the Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting. In patients not responding to allopurinol, the current standard of care, 33 percent to 49 percent of patients taking different doses of BCX4208 plus allopurinol, reached the goal of lowering serum uric acid (sUA) below 6 mg/dL at day 85, compared to 18 percent of patients taking allopurinol alone.

By contrast, between 63 percent and 79 percent of patients taking allopurinol combined with Ardea's lesinurad at different doses managed to reach the target level after just 28 days, compared to 25 percent taking allopurinol alone. (See BioWorld Today, Jan. 21, 2011.)

While the efficacy data clearly favor Ardea's compound, Jon Stonehouse, BioCryst's President and CEO, still sees a place for BCX4208 in treating the 50 percent to 80 percent of patients that aren't able to get to their sUA goal on allopurinol alone. "Clearly physicians need more choices to adequately treat the disease," Stonehouse told BioWorld Insight.

And the size of that market is growing. Doctors have realized that high uric acid levels can be destructive to joints and the kidneys and are associated with hypertension. An estimated 9.6 million patients in the U.S. alone will be diagnosed with gout in 2015, which should open the market to new treatments. "People are realizing that not only is [the number of gout patients] growing at a rapid rate, but it's more serious than previously thought," Stonehouse said. "It's a much more serious disease than just pain in the big toe."

Comorbidities may play an integral role in selecting the gout treatment preferred by doctors. In BioCryst's study, more than half of the patients were taking a hypertension drug and 15 percent to 20 percent had diabetes. BioCryst believes doctors may be willing to sacrifice efficacy if it means avoiding drug-drug interactions between gout treatments and drugs the patients are already taking.

The novel mechanism of action of BCX4208 – it inhibits purine nucleoside phosphorylase, which is in the pathway that produces uric acid, high levels of which cause gout – could help treat patients taking drugs for other problems. "We see synergy in its use with allopurinol and that's important from a clinical perspective because you can use low doses of both drugs and get better efficacy," Stonehouse said. Lower drug doses could decrease the potential for interactions with other drugs.

Oppenheimer analyst Bret Holley agreed with the rational. "Importantly, given the number of comorbidities in gout, '4208's low drug-drug interactions may be a meaningful differentiator vs. competitors," he wrote in a research note.

BCX4208 may also fit into a niche of gout patients with kidney stones. In the literature, 20 percent to 40 percent of patients have either a clinical history of kidney stones or microscopic crystals in their kidneys that might form into a kidney stone. While BCX4208 has proven safe thus far to treat patients with kidney stones, Ardea excluded patients with a history or suspicion of kidney stones from its Phase II program because lesinurad works by encouraging the excretion of uric acid in urine, which can cause kidney stones.

Given the potential size of the gout market, BioCryst plans to find a partner to help develop BCX4208 further. In keeping with the safety-is-important mantra, the firm plans to release six-month data from an extension of the Phase II study in January. Potential partners "want as much information as they can get around safety, so the longer exposure you have, I think, the better in terms of your ability to partner," Stonehouse said.

BioCryst and Ardea are not the only players hoping to find a niche in the gout market. Metabolex Inc. recently started a Phase II trial with arhalofenate, a PPAR gamma agonist that was previously being studied for diabetes.