(Corrects patient population which responds to febuxostat in 16th paragraph of story originally published Feb. 14.)
In 1785, the caricaturist Henry William Bunbury declared strong drink, aided by a demon, as the cause of the painful inflammatory disease known as gout. Two hundred years later, AstraZeneca Plc (AZN) may be on the verge of winning approval for a more effective treatment for the malady.
Gout is having a resurgence, fueled by increasing rates of obesity and poor diet. The number of U.K. cases soared 64 percent from 1997 to 2012, according to a study in the journal Annals of the Rheumatic Diseases, while in the U.S. 8.3 million people, or 4 percent of the population, had the illness in 2011, according to a study.
The current class of drugs, which includes one that has been used for more than 50 years, doesn’t work in all patients, Michael Naughton, a rheumatologist at Ealing Hospital in London, said in an interview. Existing treatments also have side effects such as rashes that deter their use. Doctors often prescribe over-the-counter anti-inflammatories or prescription corticosteroids.
Drug companies see opportunity: AstraZeneca hopes to win regulatory approval this year for a gout drug called lesinurad, while Pfizer Inc. (PFE:US) last year bought rights to a medicine in early-stage testing. While the market is relatively small, since many of the products used to treat the disease are generic or non-prescription, lesinurad alone may have peak sales of $1 billion a year, analysts at JPMorgan Chase & Co. forecast last month.
“The pharmaceutical industry has realized that this is an area for development,” said Naughton, who is also London regional chair for the British Society for Rheumatology. “For so long we’ve had drugs that were useful but limited.”
Gout is a form of arthritis that isn’t fatal though can be agonizing. The condition is caused by a buildup of a waste product in the blood called uric acid, which is normally eliminated from the body through urine, according to the U.K.’s National Health Service. Uric acid can cause needle-like crystals to form, which seep into joints and cause inflammation.
The new drugs help patients excrete uric acid through the kidneys by blocking a protein that otherwise would cause the body to reabsorb the acid. Existing treatments prevent the release of a substance called xanthine oxidase that helps in the formation of the acid.
While genetics play a role, obesity, high blood pressure, high cholesterol, and medications such as diuretics and niacin can increase people’s risk for developing gout. Foods that can contribute to higher uric acid levels include pork, beef, seafood and liver. Alcohol also interferes with the removal of uric acid from the body.
About 17.7 million people worldwide will have the condition by 2021, according to research firm Decision Resources Group.
“It’s one of the most misunderstood and neglected diseases we have,” said James Mackay, head of AstraZeneca’s gout program. The London-based drugmaker acquired his employer, Ardea Biosciences Inc., for $1.26 billion in 2012 to gain lesinurad as well as experimental cancer drugs. Ardea also is developing a second, more potent treatment called RDEA3170 to treat elevated levels of uric acid, or hyperuricemia.
Pfizer’s drug, licensed in December from Japan’s Kissei Pharmaceutical Co. (4547), is in an early-stage clinical trial in Japan, the New York-based company said in an e-mail. Pfizer’s Neusentis research unit, which is focused on pain and sensory disorders, will handle future development of the medicine, which is known as KUX-1151, the company said.
One of the standard treatments for gout is a generic drug called allopurinol that was approved in the U.S. in 1966. The other is febuxostat, marketed by Takeda Pharmaceutical Co. in the U.S. as Uloric and by Ipsen SA and others in Europe as Adenuric and approved in the U.S. in 2009.
While febuxostat doesn’t work in every patient, it is “significantly more efficient” than allopurinol, Didier Veron, a spokesman for Ipsen, said in an e-mail.
While different in molecular structure, both allopurinol and febuxostat aim to lower the level of uric acid. Takeda also acquired Colcrys, or colchicine, which is used to treat and prevent gout flares.
AstraZeneca is testing lesinurad in combination with allopurinol compared with allopurinol alone in two late-stage trials that should yield data mid-year. The company is also testing the once-daily pill in combination with febuxostat in patients who already have crystals formed in their joints.
The new treatments may be most effective when used in combination with the old treatments, Naughton said. Some patients don’t respond to existing drugs or are allergic to them, and one-quarter of patients on febuxostat don’t achieve the desired levels or uric acid, he said.
When lesinurad was tested on its own against placebo, some patients reported serious kidney problems as well as diarrhea, nausea and constipation. A combination therapy of lesinurad with xanthine oxidase inhibitors may be the most effective way to treat patients, Briggs Morrison, AstraZeneca’s chief medical officer, told analysts on Feb. 6.
“This is very much a chronic disease but one that can be controlled if you continue to take the medication on a daily basis after the disease has been diagnosed,” Mackay said.
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