New Gout Drug Gets FDA Panel Nod
Uloric, First New Gout Drug in 40 Years, Recommended for FDA Approval
By
Daniel J. DeNoon
WebMD Health News
Reviewed By
Louise Chang, MD
Nov. 24, 2008 -- Uloric should be the first new gout drug to be approved in over 40 years, an FDA
expert panel recommends.
Currently, allopurinol (trade name, Zyloprim) is the only FDA-approved drug
that prevents formation of the uric acid crystals that cause gout. However,
side effects -- including potentially fatal reactions -- limit the amount of
allopurinol that can be tolerated. Most gout patients do not receive fully
effective doses of allopurinol.
In clinical trials sponsored by Takeda, Uloric's manufacturer, an
80-milligram dose of Uloric worked better than allopurinol; a 40-milligram dose
worked at least as well as allopurinol.
Unlike allopurinol, very little Uloric is excreted through the urine, making
Uloric safe for patients with kidney problems. Gout patients with impaired
kidney function have to take very low doses of allopurinol, making the drug
even less effective for these patients.
In 2005, the FDA refused to approve Uloric because there were slightly more
deaths and heart problems in patients taking the drug than in patients taking
allopurinol. As people with gout problems already are at higher risk of
heart disease, the FDA issued an "approvable" letter, noting that
Uloric could be approved if this safety question were addressed.
Takeda then performed a large new phase 3 clinical trial that enrolled more
gout patients than the two previous phase 3 trials combined. The new study
found no more deaths and no more heart problems in patients taking Uloric than
in patients taking allopurinol.
Based on the safety and efficacy data, the FDA panel recommended by a 12-0
vote that the FDA approve Uloric at both the 40-milligram and 80-milligram
doses. Takeda suggests the higher dose is more effective in subjects with more
severe gout.
Takeda has offered to continue studying Uloric after FDA approval. A phase 4
clinical trial would compare Uloric to allopurinol for the reduction of gout
flare-ups.
And because drugs with the same
mechanism of action as Uloric and allopurinol may affect theophylline bronchodilators, Takeda has agreed to conduct a postmarketing phase 1 study
of Uloric's interactions with theophylline.
Gout occurs when blood levels of uric acid rise. At blood levels above 7
mg/dL -- and above 6 mg/dL in the extremities -- uric acid forms crystals that
lodge in the joints and other body tissues. These crystal deposits provoke an
immune response that results in extremely painful swelling and in inflammatory
arthritis that can permanently destroy the joints.
About 1.4% of men and 0.6% of women have gout. But prevalence rises with
age. After age 80, about 9% of men and 6% of women develop gout.
The body converts a chemical called xanthine into uric acid via an enzyme
called xanthine oxidase or XO. Allopurine and Uloric each inhibit XO and
prevent the formation of uric acid.
Allopurinol is approved in doses up to 800 milligrams. However, it's rarely
dosed above 300 milligrams per day and is often ineffective. Allopurinol side
effects include upset stomach, headache, diarrhea, and
rash. Although rare, allopurinol hypersensitivity syndrome can develop.
It's fatal 20% to 30% of the time.
The most common side effects seen in patients taking Uloric during clinical
trials were upper respiratory tract infections, muscle and connective-tissue
symptoms, and diarrhea. The drug was well tolerated, and these side effects did
not increase over long-term use.
SOURCES: FDA, "Briefing Document for the Arthritis Advisory Committee Meeting,
Uloric/febuxostat," Nov. 24, 2008. Takeda Pharmaceuticals North America Inc., "Briefing Document for
Advisory Committee, Division of Anesthesia, Analgesia, and Rheumatology
Products," Nov. 24, 2008.
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