AstraZeneca (AZ) has reported additional late-stage data for its gout candidate lesinurad that should support its plans to file for approval this year.
The company now has positive data from three phase III studies of lesinurad – a selective uric acid re-absorption inhibitor (SURI) – in combination with xanthine oxidase inhibitors, which are among the most commonly-used drugs to treat the painful condition.
In gout, uric acid crystals are deposited in the joints, creating symptoms similar to an acute arthritis flare. Lesinurad stimulates uric acid excretion from the body to reduce blood levels and prevent crystals being formed.
Two trials – CLEAR1 and CLEAR2 – compared two doses of lesinurad (200mg and 400mg once daily) in combination with the XO inhibitor allopurinol in patients who could not reach their target serum uric acid levels on allopurinol alone.
A third study looked at the combination of lesinurad with Takeda’s Uloric (febuxostat), which when it launched a few years back was the first new drug for gout in four decades.
At a dose of 400mg, lesinurad achieved its objective of increasing the proportion of patients meeting serum uric acid targets in all three of the studies, reinforcing the results of an earlier trial – called LIGHT – that was reported towards the end of last year.
The 200mg dose showed a significant improvement in the allopurinol studies, but failed to do so in the febuxostat at month six, the primary endpoint in the trial.
Given that the combination was significantly superior at all other time points, however, AZ says it is confident it can proceed with regulatory filings for the lower dose, particularly as the incidence of renal-related adverse events and kidney stones was higher with lesinurad 400mg plus an XO inhibitor.
Chief medical officer Briggs Morrison said there is a significant unmet treatment need in gout, with 40 to 70 per cent of patients not reaching target uric acid levels with current drugs.
“These data indicate that combination therapy with lesinurad may be a potential treatment option for gout patients,” he added.
AZ acquired lesinurad as part of its $1bn takeover of Ardea Biosciences in 2012. The drug is seen as something of a wildcard in the company’s pipeline, because while the number of patients around the world is very large at around 15 million, uptake of new therapies is hard to gauge.
Uloric has become a nice seller for Takeda with sales of around $450m – around $260m of that total coming from the US – but is already facing patent challenges from generic competitors. On the other hand, another recent entrant into the market – Savient Pharmaceuticals – was forced to file for bankruptcy last year on lacklustre sales of its gout therapy Krystexxa (pegloticase).
Decision Resources recently predicted however that the gout market will reach around $1bn in the US, Japan and the largest EU markets (France, Germany, Italy, Spain and the UK) in 2018, with lesinurad and BioCryst’s purine nucleoside phosphorylase (PNP) inhibitor ulodesine expected to drive growth.