AZ's gout drug shows good safety
New Phase III data for AstraZeneca's gout drug lesinurad have backed its efficacy and seem to address earlier concerns about its safety.
Last year, AZ reported the results of the Phase III LIGHT trial of lesinurad which indicated that - while the selective uric acid re-absorption inhibitor (SURI) was effective in reducing serum uric acid (sUA) levels in patients with gout, the drug did seem to be linked to adverse effects on the kidney.
AZ has speculated that use of the drug as a combination with established gout drugs such as xanthine oxidase (XO) inhibitors would tackle the problem and, the results of three new Phase III trials seem to back up that position.
Gout is a massively painful condition in which high levels of sUA in the blood cause some to be deposited in crystalline form in the joints, creating arthritis-like symptoms. Lesinurad is designed to stimulate excretion of UA from the body and reduce levels in the blood.
Two of the new trials of lesinurad - CLEAR1 and CLEAR2 - compared two doses of the drug (200mg or 400mg once-daily) to placebo on top of background therapy with generic allopurinol in patients who could not achieve effective reduction in sUA on allopurinol alone. In both trials, the addition of AZ's drug increased the proportion of patients achieving target sUA levels.
A third trial - called CRYSTAL - looked at the combination of lesinurad or placebo with Takeda's $450 million-a-year XO inhibitor Uloric (febuxostat) and also found that the drug achieved a significant increase in the proportion of sUA responders - almost across the board.
The only anomaly in the data was that the lower (200mg) dose failed to do so at the six-month timepoint, although it was significantly better than Uloric alone at all other time points in the trial.
On the critical issue of safety, the incidence of renal-related adverse events - including kidney stones - with lesinurad 200mg was comparable to placebo when given alongside an XO inhibitor. The incidence of renal-related adverse events and kidney stones was however higher with the 400mg dose.
Filing before year-end?
AZ chief medical officer Briggs Morrison said earlier this month the company that a placebo-like renal adverse event profile for lesinurad would be "brilliant" and even a slight difference from placebo would "still be an important profile."
The expectation now is that the company can press ahead with filing the 200mg dose as a combination therapy later this year in both the US and Europe.
"There is a significant unmet need, with 40% to 70% of gout patients not reaching target levels of sUA with the current standard of care," he said. "These data indicate that combination therapy with lesinurad may be a potential treatment option for gout patients."
Lesinurad was acquired by AZ as part of its $1bn takeover of Ardea Biosciences in 2012, which also included a second-generation SURI, called RDEA3170, which in preliminary studies looks to have a better renal safety profile than its sister compound.
Market research firm GlobalData recently estimated that the gout market will increase in size from $989 million in six major global pharma markets (the US, France, Germany, Italy, Spain and the UK) to $2.28 billion, as new therapies expand the market.
It predicts lesinurad, along with BioCryst's purine nucleoside phosphorylase (PNP) inhibitor ulodesine and Novartis' new anti-inflammatory Ilaris (canakinumab; already approved for gouty arthritis), will drive the growth in the market.
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