Gout Treatment News
Dealing with gout — the malady of kings
OAK RIDGE, Tenn. —
Gout is the most common type of inflammatory arthritis in the United States and the number of cases has doubled in the last two decades. An attack usually involves a single joint in the legs or feet, particularly the big toe, and may cause severe pain for up to a week.
At the heart of gout is a class of molecules called “purines.” Most purines are part of the structure of DNA and because DNA is found in cells, cellular foods like meat have a lot of purines. When purines are broken down into uric acid, it may accumulate in a joint and create symptoms of pain, redness, and swelling.
Impaired uric acid excretion by our kidneys is worsened by many prescription and some over-the-counter drugs. Diuretics and low-dose aspirin are the big offenders. High-fructose sweeteners and alcohol are food sources that also impair uric acid excretion.
Diabetes and a pre-diabetic condition called “metabolic syndrome” are now epidemic in the United States. These conditions contribute to gout by both altering uric acid metabolism and by creating renal insufficiency. Sixty percent of gout sufferers now have metabolic syndrome.
There is often no relationship between blood levels of uric acid and the timing of an acute attack of gout. For diagnosis, the best strategy is to have your doctor perform testing two weeks after the attack.
At that time, if your blood level of uric acid is elevated, you likely have gout. The diagnosis is unlikely if the level is less than 4 mgj dl. In the event of a positive diagnosis, you probably have a problem excreting uric acid instead of overproducing it if your 24-hour urine uric acid is less than 800 mg.
Treatment of an acute gout attack is often best handled with early use of a non-steroidal, anti-inflammatory drug like indomethacin. Colchicine is a drug that has been used for gout in one form or another for centuries but has only recently been approved by the FDA for this purpose. Two pills at onset of symptoms and one more in two hours is all that should be used. Higher doses do not work better and may have toxic effects. Oral or intramuscular steroids may also be helpful.
A drug called probenecid helps promote excretion of uric acid. It may be useful if someone cannot take indomethacin or colchine.
For those that have had three or more gout attacks in a given year, a preventive medicine that limits uric acid production may be helpful. Allopurinol has been widely used for this purpose. Another drug in the same category is now available. There is no good evidence that it works better and it is considerably more expensive. A new drug is in the pipeline that uses a slightly different mechanism to decrease uric acid production. Expect it to be expensive also.
Always discuss strategy with your doctor before considering medicine use, but remember, as with most maladies, the best management of gout is still prevention.
A study of 89,000 older female nurses shows that drinking one to three cups of coffee daily can reduce the risk of developing gout by 22 percent. Four cups or more can reduce the risk by 57 percent. Decaf does not carry the same risk reduction and other caffeinated drinks do not work.
Vitamin C can promote uric acid excretion by limiting its re-absorption in the kidneys. A 20-year study of 47,000 men showed that daily intake of at least 250 mg of Vitamin C was associated with fewer attacks of gout. There was a 17 percent decrease in risk for each 500 mg increase in Vitamin C consumed.
Losing weight and increasing exercise can decrease the risk of gout from diabetes and metabolic syndrome. Limiting alcohol and refined high-fructose foods like soft drinks will also significantly decrease the risk. Decreasing meat consumption, particularly organ and game meats, as well as seafood can decrease the likelihood of gout. Increasing low-fat dairy can also decrease the risk.
Moderate intake of purine-rich vegetables like spinach, beans, peas, mushrooms, oatmeal, and wheat bran have not been found to significantly increase the risk of gout.
Trauma can precipitate an attack of gout, so always protect your feet and knees.
Gout may have once been the malady of kings, but now we have another reason to live longer and healthier lives than Henry the VIII. We know what causes gout and we know how to treat it and prevent it.
Ardea Follows Positive Gout Results with $71.5M Offering
January already had been a pretty good month for Ardea Biosciences Inc. and it got even better on Thursday.
San Diego-based Ardea followed up its announcement earlier this month of positive, preliminary, top-line results from its Phase IIb study of RDEA594 in combination with the current standard of care for the treatment of gout, allopurinol, with an underwritten public offering of 2.75 million shares of common stock priced at $26 a share, about 3 percent below Wednesday’s closing price. The company expects gross proceeds of about $71.5 million.
Ardea stock (NASDAQ:RDEA) was down 56 cents, to close at $26.25 Thursday.
Ardea also earned a $15 million milestone payment earlier this month from partner Bayer HealthCare AG under a 2009 license agreement concerning MEK inhibitor compounds. Bayer’s initiation of a Phase II trial of BAY 86-9766 with sorafenib in hepatocellular carcinoma triggered the payment. The payment brought Ardea’s total under the agreement to $50 million to date, and the company could receive as much as $357 million more in future milestones. (See BioWorld Today, April 29, 2009.)
BofA Merrill Lynch and Jefferies & Co. Inc. are joint book-running managers with JMP Securities, Brean Murray, Carret & Co. and Roth Capital Partners acting as co-managers. The underwriters have a 30-day option to purchase an additional 412,500 shares to cover overallotments, which potentially could raise an additional $10.7 million. The offering is expected to close Jan. 25.
The company said it anticipates using the proceeds for clinical trial expenses – including RDEA594, which is expected to enter Phase III testing this year – research and development expenses and working capital.
John Beck, Ardea’s CFO and senior vice president finance/operations, told BioWorld Today that he expects some of the funds to go toward the Phase III program for RDEA594, but said that it is too soon to pin down specifics.
“Because we have not yet had our end of Phase II meetings with U.S. and EU regulatory authorities, we are unable at this time to provide specifics regarding the scope of our Phase III program for RDEA594,” Beck said. “However, we do believe that the proceeds from this raise, together with our existing resources, provide a strong financial foundation as we plan for Phase III.”
Beck said that the company’s preliminary, unaudited cash balance at the end of 2010 was approximately $80 million. Proceeds from the new financing, net of expenses and conservatively assuming the underwriter’s allotment is not exercised, plus the $15 million milestone payment from Bayer brings Ardea’s post-transaction cash position to approximately $162 million, less cash used in operating activities during the first few weeks of January, he said. The company plans to release its 2010 earnings and file its annual financial report on March 11.
A number of analysts have had good things to say about Ardea since the company reported that the primary and key secondary endpoints of a Phase IIb study of RDEA594 in combination with the allopurinol were achieved, with highly statistically significant reductions in serum uric acid (sUA) and up to 89 percent of patients taking a combination of RDEA594 600 mg and allopurinol reaching target sUA. Allopurinol accounts for more than 90 percent of the unit sales of chronic gout prescription medications, the company said.
Jefferies & Co. analyst Thomas Wei wrote earlier this month that RDEA594. “could become the standard-of-care for second-line gout treatment.”
Wei added that “the next major strategic decision will be whether to partner RDEA594 or retain rights through Phase III trials, a decision which we expect the company to make within the next six to 12 months.”
Leerink Swann Research analyst Joseph Schwartz wrote during the first week of January that “RDEA594 is the front-runner in the race to becoming the next new oral gout drug.”
Jonathan Aschoff, an analyst for Brean Murray, estimated “the U.S. market for RDEA594, which only includes the 60 percent of allopurinol patients that do not adequately respond to allopurinol, as about a $3 billion opportunity.”
Last week Piper Jaffray & Co. analyst M. Ian Somaiya said in a company note that after meeting with Ardea management, “we believe that Ardea will conduct two Phase IIIs to ensure sufficient data, namely safety, for approval. Furthermore, we expect key efficacy endpoints, beyond sUA reductions, to include benefit in flare rate, thus allowing a broader label and potentially encompassing all gout patients.”
Nine months ago Ardea netted proceeds of about $77.1 million in a public offering of about 4 million shares. (See BioWorld Today, April 7, 2010.)
There are limited treatment options currently on the shelves for gout. Allopurinol has been the standard of care with Osaka, Japan-based Takeda Pharmaceutical Co. Ltd.’s xanthine oxidase inhibitor Uloric (febuxostat) gaining approval early in 2009. Savient Pharmaceuticals Inc., of East Brunswick, N.J., gained FDA approval in September 2010 for Krystexxa (pegloticase), a pegylated uric acid-specific enzyme for chronic refractory gout. (See BioWorld Today, Sept. 16, 2010.)
Beyond its gout program and MEK inhibitor partnership with Bayer, Ardea also has a Phase II-stage HIV program testing RDEA806, a non-nucleoside reverse transcriptase inhibitor.